Note: Descriptions are shown in the official language in which they were submitted.
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SYSTEM AND METHODS FOR TREATING CANCER CELLS WITH
ALTERNATING POLARITY MAGNETIC FIELDS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001]This application claims the priority benefit of US Provisional
Application No.
62/802,689, filed February 7, 2019, which is hereby incorporated herein by
reference in
its entirety.
TECHNICAL FIELD
[0002]The present invention involves treating rapidly proliferating or
dividing cells, such
as cancer cells, and more specifically to systems and methods for selectively
inhibiting or
destroying rapidly dividing cells by applying an alternating magnetic field
having defined
characteristics to a target area of a patient's body. Some embodiments of the
invention
provide a wearable system capable of providing an ambulatory therapy to a non-
stationary patient by applying a magnetic field to inhibit or destroy rapidly
dividing cells to
the target body area.
BACKGROUND OF THE INVENTION
[0003] Cell division is a reproductive process in all living systems,
including without
limitation simple one-celled organisms such as bacteria and protozoa, as well
as more
complex organisms such as algae, plants, and animals, including humans. The
cell
division cycle involves a series of events within the cell that leads to a
duplication of the
DNA of the cell, with one of the duplicate DNA sequences going to each of two
daughter
cells. Prokaryotic cells are one-celled organisms that lack an enclosed
nucleus and
reproduce by a cell division process known as fission. More complex organisms
with
enclosed nuclei are called eukaryotes, whose cells asexually reproduce by a
three-part
cell division process involving periods known as interphase, mitosis, and
cytokinesis. In
the reproduction of sexual cells (i.e., egg and sperm) of more complex
organisms, mitosis
is replaced by meiosis.
[0004] During interphase, the parent cell produces nutrients and other
components
necessary for mitosis, and the DNA is duplicated as loosely packed chromatin.
Mitosis
involves separation of the duplicated DNA into nucleus of the eukaryotic cell
into two
nuclei, each having a complete copy of the duplicated DNA. In cytokinesis, the
cytoplasm,
organelles & cell membrane are divided, forming two daughter cells of roughly
equal size.
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[0005]The process of mitosis is further divided into the stages of prophase,
prometaphase, metaphase, anaphase, and telophase. In prophase, the DNA
duplicated
during interphase condenses into discrete long, thin chromosomes having two
chromatids
joined by a centromere. Each cell has two centrioles, which move to opposite
poles of
the cell during prophase. Microtubules radiate from near the two centrioles
toward the
center of the cell, including some which extend to the chromatids and help to
separate
the two chromatids into separate daughter chromatids. In metaphase, the
chromosomes
move toward the cell equator and align in the metaphase plane (or equatorial
plane). The
daughter chromatids separate from each other at the equator during early
anaphase by
moving along the microtubule spindle fibers toward the centromeres at opposite
poles of
the cell, a process which elongates the cell. In late anaphase the daughter
chromosomes
each reach their opposite poles of the cell, and the cell membrane begins to
pinch to form
the two daughter cells, which is part of cytokinesis, or the process by which
the daughter
cells are separated. During telophase, the microtubules continue to lengthen
and a new
nuclear envelope forms around each of the separated daughter chromosomes, each
of
which has an identical set of chromosomes, and cytokinesis proceeds with
further
pinching of the two daughter cells toward becoming separate entities. By the
end of
telophase, the microtubule spindles disappear. Finally, the daughter cells
fully separate,
completing cytokinesis.
[0006] Cancer cells and some non-cancerous cells (e.g., non-malignant tumors)
proliferate or grow in an uncontrolled manner in contrast to normal cells. In
addition to
the extra space such tumors or cells occupy, they may also damage nearby
normal cells.
Cancer cells may also metastasize, traveling to other locations in the body,
where they
continue to hyperproliferate and may form new tumors. The rapid growth of
tumors and
cancer cells results from their rapid rate of cell division compared to normal
cells.
[0007] Many effective anti-cancer and anti-tumor therapies are based on the
fact that cells
in the process of dividing are more sensitive to radiation and many drugs than
non-
dividing cells. Because tumor cells divide much more frequently than normal
cells, it is
possible, by using therapies that act on tumor cells while they are dividing,
to selectively
damage or destroy them while leaving normal cells¨which divide less
frequently¨less
affected. However, because many types of cancer cells are only slightly more
susceptible
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to radiation and/or chemotherapy agents than normal cells, it is not always
possible to
selectively affect tumor cells while leaving normal cells unaffected.
Consequently, many
radiation and chemotherapy agents significantly damage normal cells as well as
tumor
cells, leading to a significant patient burden (e.g., pain, scarring, organ
damage, blood
damage, impaired immune system function, etc.) for even "successful"
treatments.
[0008] In addition to radiation and chemotherapeutic agents, other therapies
involving
different modes of action have been used to treat tumor cells, including
without limitation
ultrasonic and electrical therapies. Electrical currents and electrical fields
have been used
for decades for medical purposes.
[0009] One type of electrical therapy involves applying an electrical current
through body
tissue separated by two or more conductive electrodes. This type of therapy
may be
used, for example to stimulate or excite muscle or nerve tissue (e.g.,
pacemakers,
defibrillators, neurostimulators) or to generate heat within desired body
tissue circuit (e.g.,
thermal therapies to remodel collagen or to ablate tissue). Electrical
therapies involving
conductive electrodes may involve direct current or alternating current at a
wide range of
frequencies (e.g., less than 1 Hz to above 1 MHz). The energy from electrical
currents is
delivered to tissue based on the electrical conductive characteristics (e.g.,
resistance,
capacitance) of the tissue. Since these properties are similar for both tumor
and normal
cells, such therapies affect both tumor and normal cells (e.g., destroying
both by heat if
they are within the current path) in the same manner. At lower frequencies
(typically
below 20 kHz, the use of conductive electrodes may be used to stimulate muscle
or nerve
tissue to activate muscle or nerve fibers. At frequencies used in many
electrical therapies
(e.g., tens of kHz to MHz), stimulation with conductive electrodes is too
rapid for
stimulation signals to propagate through such tissue and the signals are
"shorted."
[0010] Another medical use of electrical energy involves the use of insulated
electrodes
to deliver high frequency electrical energy radiatively or inductively to
target tissue. For
example, radio frequency (RF) or microwave energy may be applied radiatively
to tissue
through the air or another electrically insulating material separating the
electrodes from
the tissue being treated. The effect of this type of electrical energy on
living tissue is
based on the dielectric properties of the tissue rather than their conductive
characteristics.
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[0011] More recently, insulated electrodes have been used to treat cancer
cells and other
rapidly proliferating cells by applying AC electric fields at frequencies of
50-500 kHz and
electric field strengths of about 10 - 1000 V/m to a target body area that
includes such
cells. Such therapy is often referred to as TC ("tumor curing") field or TTF
("tumor
treatment field") therapy. In US 6,868,289, which is hereby incorporated by
reference in
its entirety, a method and apparatus are disclosed for destroying rapidly
proliferating cells
using insulated electrodes to generate an electric field. At electric field
frequencies of 50-
500 kHz, the cell membranes of the dividing cells act to concentrate the
electric field lines
at the cleavage furrow separating the two daughter cells of the dividing cell.
The high-
density field at the cleavage furrow causes polarized or charged intracellular
components
within the cell to move toward the high-density field lines at the cleavage
furrow,
eventually disrupting the cell membrane at the cleavage furrow, and destroying
the diving
daughter cells.
[0012] In US 8,019,414, which is hereby incorporated by reference in its
entirety, a
method of killing or destroying cancer cells is disclosed that involves
applying an electric
field together with another cancer therapy such as radiation or chemotherapy
drugs. The
electrical field may be a field such as that disclosed in the '289 patent.
[0013] The use of electric fields to destroy cancer cells, while effective at
certain
frequencies and electrical field strengths, is limited in many practical
respects. To provide
a safe and consistent electrical field strength, the electrodes of systems
such as those
disclosed in the '298 and '414 patents must be in intimate contact with the
tissue (e.g.,
skin) of the patient at all times during the treatment. To ensure good contact
with the
patient's skin, it may be necessary to shave all hair from the skin to which
the electrodes
are coupled. Because the therapy may be delivered for an extended period of
time, the
electrodes frequently cause skin irritation at the electrode contact site. For
example, in
one recent study of TTF therapy, forty-three percent (43%) of patients
experienced some
skin irritation, with 1`)/0 reporting severe skin irritation. The relatively
high incidence of skin
irritation or pain may prohibit the therapy in sensitive body areas (e.g.,
breast tissue, etc.).
TTF therapy also involves the use of relatively high voltages. For this
reason, patients
must be careful in performing everyday activities having a risk of water
exposure (e.g.,
showering, exercise (sweating), or even exposure to rain.
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[0014]The use of electrodes in direct contact with the patient's skin presents
a risk of
burning or heating of tissue adjacent to the electrodes. Because of this risk
(and buildup
of dirt, oils, etc.), the electrodes in TTF therapy systems typically require
frequent
replacement (e.g., twice each week). Patients wearing TTF electrodes on the
scalp
reported headaches related to wearing the electrodes 24 hours a day.
[0015]TTF electrodes must also be placed by trained users (e.g., technicians
or
physicians). Because the treatment is highly localized (i.e., between the
electrodes),
precise location of the cancer/tumor must first be performed, and the
electrodes must be
placed with a high degree of accuracy to create an electric field that passes
through it. If
the electrodes a slightly off of optimal placement, the treatment may result
in suboptimal
results.
[0016] In addition, although the '289 patent discloses ambulatory embodiments
(i.e.,
embodiments in which the patent can wear and use the system in performing at
least
some ordinary non-stationary life activities such as walking, driving,
shopping, etc.), in
practice the power requirements (e.g., high voltages) for generating
appropriate electric
fields (e.g., at least 10 V/m) result in bulky and/or heavy electronics boxes
that must be
coupled to the electrodes and thus carried by the patient. One clinical study
showed a
relatively high rate of falls in patients carrying these cumbersome TTF
electronics boxes.
[0017] In view of these limitations to TTF systems, there is a need for safer
therapies that
may be applied for longer durations to destroy cancer or other rapidly-
dividing cells. The
many problems associated with electrodes also raise a need for new therapies
that avoid
a risk of skin pain or the need for continuous contact with skin or other
tissue. Because
the efficacy of the system depends upon how long the electric fields can be
applied to the
rapidly-dividing cancer cells, less bulky, heaving, and cumbersome systems are
needed
to permit truly ambulatory, long duration treatments. Finally, there is a need
for therapy
systems that do not require trained patients or clinicians for setup.
SUMMARY
[0018] In one aspect, the present invention provides a method of treating
cancer cells in
a target body area of a patient's body comprising: coupling a magnetic field
generator to
the target body area of the patient's body; and applying an alternating
polarity (AP)
magnetic field to the target body area using the magnetic field generator, the
AP magnetic
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field having a frequency of 0.5 - 500 kHz and a magnetic field strength of
0.05 - 5 milliTesla
(mT), wherein the AP magnetic field selectively affects the cancer cells to
achieve at least
one of damaging the cancer cells, inhibiting the growth of the cancer cells,
reducing tumor
size, inhibiting angiogenesis, or preventing metastasis of the cancer cells,
while leaving
non-cancer cells substantially unharmed.
[0019] In another aspect, the present invention provides a system for treating
cancer cells
in a target body area of a patient's body comprising: at least one alternating
polarity (AP)
electromagnetic coil coupled to a target body area of the patient's body; a
power supply
for supplying power to said at least one AP electromagnetic coil; and a
controller for
controlling the at least one AP electromagnetic coil and power supply to
generate and
apply to the target body area an AP magnetic field having a frequency of 0.5 -
500 kHz
and a field strength of 0.05 - 5 mT, wherein the AP magnetic field selectively
affects the
cancer cells to achieve at least one of damaging the cancer cells, inhibiting
the growth of
the cancer cells, reducing tumor size, inhibiting angiogenesis, or preventing
metastasis
of the cancer cells, while leaving non-cancer cells substantially unharmed.
[0020] In another aspect, the present invention provides a system for treating
cancer cells
in a target body area of a patient's body comprising: at least one alternating
polarity (AP)
electromagnetic coil coupled to a target body area of the patient's body; a
retaining
element to which the at least one AP electromagnetic coil is coupled, wherein
the retaining
element is adapted to maintain the at least one AP electromagnetic coil in a
desired
position relative to the target body area; a power supply for supplying power
to said at
least one AP electromagnetic coil; and a controller for controlling the at
least one AP
electromagnetic coil and power supply to generate and apply to the target body
area an
AP magnetic field having a frequency of 0.5 - 500 kHz and a field strength of
0.05 - 5 mT,
wherein the AP magnetic field selectively affects the cancer cells to achieve
at least one
of damaging the cancer cells, inhibiting the growth of the cancer cells,
reducing tumor
size, inhibiting angiogenesis, or preventing metastasis of the cancer cells,
while leaving
non-cancer cells substantially unharmed.
BRIEF DESCRIPTION OF THE DRAWINGS
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[0021] Figure 1 is a schematic block diagrams of a system for providing an
alternating
polarity (AP) magnetic field to a target body area of a patient's body,
according to one
embodiment for selectively destroying cells.
[0022] Figure 2 is a front view of a retaining element comprising a bra having
one or more
AP electromagnetic coils for providing an AP magnetic field to breast tissue,
according to
one embodiment of the invention.
[0023] Figure 3 is a front view of a retaining element comprising a hat
including one or
more AP electromagnetic coils for providing an AP magnetic field to brain
tissue,
according to one embodiment of the invention.
[0024] Figure 4 is a front view of a retaining element comprising a shirt
having one or
more AP electromagnetic coils for providing an AP magnetic field to thoracic
or abdominal
tissue, according to one embodiment of the invention.
[0025] Figure 5 is a front view of a retaining element comprising a neck cuff
or collar
having one or more AP electromagnetic coils for providing an AP magnetic field
to a target
area of a patient's body, according to one embodiment of the invention.
[0026] Figure 6 is a front view of a retaining element comprising a bandage
having one
or more AP electromagnetic coils for providing an AP magnetic field to a
target area of a
patient's body, according to one embodiment of the invention.
[0027] Figure 7A is a photograph at 10X magnification of untreated B16F10
mouse
melanoma cells incubated for 24 hours.
[0028] Figure 7B is a photograph of B16F10 mouse melanoma cells exposed to an
AP
magnetic field for 24 hours according to one embodiment of the invention.
[0029] Figure 8 is a bar graph showing the reduction in cell counts of B16F10
mouse
melanoma cells treated with an AP magnetic field for 24 hours compared to
untreated
controls.
DESCRIPTION
[0030] Exemplary embodiments of the present disclosure are illustrated in the
drawings,
which are illustrative rather than restrictive. No limitation on the scope of
the technology
or on the claims that follow is to be implied or inferred from the examples
shown in the
drawings and discussed here.
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[0031] In some embodiments, the invention provides apparatus and methods for
treating
a patient having cancer or other rapidly dividing cells (e.g., bacterial
infection) in a target
body area using alternating polarity (AP) magnetic fields at specified
frequencies to
destroy or inhibit the proliferation of the rapidly dividing cells. The use of
electric fields,
including without limitation TTF systems, to treat patients having cancer or
other diseases
characterized by rapidly-dividing cells has a number of limitations that make
treatment for
some patients difficult, ineffective, painful, or unsafe. Embodiments of the
present
invention overcome one or more of these limitations by using AP magnetic
fields to treat
rapidly-dividing or hyperproliferating cells.
[0032] As used herein, the terms "magnetic field tumor (MFT) therapy" and
"MFTT" refer
to systems and methods for treating cancer or other rapidly-dividing cells
with AP
magnetic fields at specified frequencies and magnetic field strengths to
destroy or inhibit
the proliferation of such cells. In various embodiments, the present invention
may be
used to treat one or more cancers such as throat cancer, thyroid cancer, mouth
cancer,
nose cancer, salivary gland cancer, lung cancer, lung carcinoid tumors, throat
cancer,
thyroid cancer, mouth cancer, nose cancer, salivary gland cancer, lung cancer,
lung
carcinoid tumors, thymic malignancies, tracheal tumors, pancreatic cancer,
liver cancer,
stomach cancer, kidney cancer, ovarian cancer, prostate cancer, ovarian
cancer, colon
cancer and rectal cancer.
[0033] Figure 1 is a simplified schematic block diagram illustrating certain
components of
an MFT therapy system 100 according to an embodiment of the invention. The MFT
therapy system 100 includes an alternating polarity magnetic field generator
(APMFG)
110 to generate an electrical signal to energize one or more alternating
polarity (AP)
electromagnetic coils 120 to produce an AP magnetic field having specified
frequency
and field strength characteristics. In one embodiment, the AP electromagnetic
coils 120
may have sizes and shapes adapted to engage one or more target body areas of a
patient
(e.g., torso, breast, head, neck, throat) for treatment of cancer or
hyperproliferating cells
in the target body area. The electrical signals generated by APMFG 110 and
applied to
AP electromagnetic coils 120 is controlled by a controller 130, which
specifies the
parameters of the magnetic fields to be generated by APMFG 110 and AP
electromagnetic coils 120, and controls the function and operation of the
system 100. An
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interface 140 is provided to allow a user to specify treatment parameters to
be
programmed or communicated to the controller 130, and to receive information
from the
controller relating to the operation and status of the MFT therapy system 100.
A power
supply 150 provides power to MFT therapy system 100. Power supply 150 may be
selected from a variety of known power supplies, and may comprise, in various
embodiments, a battery such as a disposable or rechargeable battery, or a
power source
such as a standard 120V, 60 Hz electrical power outlet in the US, together
with circuitry
for regulating the power at appropriate currents and voltages for each of the
APMFG 110,
AP electromagnetic coils 120, controller 130, and interface 140.
[0034] Controller 130 may include circuitry and other components (e.g.,
microcontrollers,
resistors, registers, memory, firmware, software, etc.) to direct and control
the operations
of the APMFG 110, AP electromagnetic coils 120, and interface 140. Figure 1
illustrates
an embodiment in which the AP electromagnetic coils 120 are energized directly
from the
magnetic field generator. In an alternative embodiment (not shown), controller
130 may
communicate directly with each of the one or more AP electromagnetic coils 120
to control
their operation in whole or in part (e.g., by switches that enable or disable
each AP
electromagnetic coil 120).
[0035] Controller 130 includes a timing control module 112 for controlling the
timing of the
MFT therapy delivered by AP electromagnetic coil(s) 120 to one or more target
body
areas or tissues. In various embodiments, timing control module 112 may cause
the AP
magnetic field generator 110 and AP electromagnetic coils 120 to provide MFT
therapy
for a programmed duration such as 1-100 hours or other treatment period, or
the timing
of and between a plurality of therapy treatment periods. For example, the
timing control
module 112 may implement a first therapy for a first time period (e.g., during
waking hours
of the patient) at a first frequency and field strength), followed by a second
time period in
which no therapy is applied, followed by a third time period in which a second
therapy at
a second frequency and second field strength. Timing module may also control
the timing
of changes in other treatment parameters, such as changes in the frequency or
field
strength of the MFT therapy applied to the patient.
[0036] A frequency control module 114 controls the frequency of the AP
magnetic fields
delivered by AP electromagnetic coil(s) 120 to the one or more target body
areas or
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tissues. Frequency control module 114 may control the frequency of the AP
magnetic
field at a programmed frequency of 0.5 - 500 kHz. In some embodiments, the
frequency
control module 114 may control frequency changes to the AP magnetic fields
generated
by the APMFG 110 and the AP electromagnetic coils 120 at a programmed rate of
change
or according to specific frequency step changes.
[0037]A magnetic field strength control module 116 controls the field strength
of the AP
magnetic fields applied to the one or more target body areas. Magnetic field
strength
control module 116 may control the field strength at a programmed magnetic
field strength
of 0.05 - 5 mT, and may control changes in the field strength according to a
programmed
rate of change or programmed step changes in field strength.
[0038] Controller 130 may include programming logic, timers, and other
circuitry to
accomplish the functions of the timing control module 112, frequency control
module 114,
and magnetic field strength control module 116.
It will be appreciated in alternative
embodiments, the functions of all or portions of timing control module 112,
frequency
control module 114, and magnetic field strength control module 116 may be
combined
into one or more submodules, or implemented by controller 130 as a whole.
[0039] In one embodiment, interface 140 may include a user input, such as a
keyboard
or buttons, to allow a user to input or receive data from controller 130.
In a further
embodiment (not shown,) interface 140 may be located within controller 130 and
may
comprise a transceiver to communicate with a separate user device (not shown)
such as
a cell phone, tablet, or other computing device to program the MFT therapy
system 100
and receive data therefrom (e.g., operating and alarm status flags, programmed
parameters, treatment time, etc.). In other alternative embodiments (not
shown),
interface 140 may be omitted, or may be incorporated as part of a single unit
having some
or all of the functions of AP magnetic field generator 110, controller 130,
and interface
140.
[0040] Referring again to Figure 1, in various embodiments the APMFG 110 may
provide an electrical signal to cause each of the one or more AP
electromagnetic coils
120 to generate magnetic fields having one or more fixed or variable AP
frequencies.
Although shown in the simplified schematic diagram of Figure 1 as coupled to
APMFG
110 by a single wire, it will be understood that each of AP electromagnetic
coils 120 will
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generally be coupled to APMFG 110 by a pair of wires (not shown) to provide a
complete
circuit. In fixed-frequency embodiments, APMFG 110 may cause each of the one
or more
AP electromagnetic coils 120 to generate a magnetic field having a single
frequency or a
plurality of frequencies either continuously or intermittently according to a
defined duty
cycle (e.g., having a programmable on-time during which the magnetic field is
emitted
from AP electromagnetic coils 120, followed by an off-time during which no
field is
emitted). The APMFG 110 may also cause the one or more AP electromagnetic
coils
120 to generate AP magnetic fields having a variety of waveforms, e.g.
sinusoidal,
triangular, trapezoidal etc. In some embodiments the APMFG110 may cause the
one or
more AP electromagnetic coils 120 to generate AP magnetic fields having a pre-
defined
number of waveforms of a specified first frequency, and repeat this pattern at
a second
specified frequency (burst mode). In other embodiments, the APMFG 100 may
cause the
one or more AP electromagnetic coils 120 to generate a magnetic field having a
waveform
which uses a fixed frequency or a combination of frequencies coupled with
amplitude
modulation.
[0041] Whether fixed or variable, the frequency (or frequencies) of the AP
magnetic fields
generated by each AP electromagnetic coil 120 are preferably frequencies below
about
1 MHz, and more preferably are frequencies within the range of 0.5 ¨ 500 kHz,
more
preferably within the range of 25 ¨ 400 kHz, and still more preferably within
the range of
100 ¨ 300 kHz. In one embodiment, the MFT therapy system 100 may comprise at
least
two AP electromagnetic coils 120, each having a fixed or variable frequency
within a
different frequency range to provide magnetic fields at multiple frequencies
to a target
body area or tissue. For example, APMFT 110 may generate a first electrical
signal to
cause a first AP electromagnetic coil 120 to generate an AP magnetic field
with a first
fixed frequency or a variable first frequency within a first frequency range,
and a second
electrical signal to cause a second AP electromagnetic coil 120 to generate an
AP
magnetic field with a second fixed frequency or a variable second frequency
within a
second frequency range, where both the first frequency range and the second
frequency
range are ranges within the range of 0.5 ¨ 500 kHz. As a nonlimiting example,
the first
range may be a low-frequency range (e.g., 1 ¨ 5 kHz) and the second frequency
range
may be a higher-frequency range (e.g., 50 kHz ¨ 300 kHz).
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[0042] Without being bound by theory, it is believed that AP magnetic fields
within a
plurality of frequency sub-ranges within the range of 0.5 ¨ 500 kHz may affect
different
aspects of the reproduction cycle of rapidly-dividing cells, and that each
such aspect may
be more strongly affected by AP magnetic fields within a particular frequency
sub-range
within the broader range of 0.5 ¨ 500 kHz. For example, the interruption of
angiogenesis
by extremely low frequency AP magnetic fields has been reported for AP
magnetic fields
having a frequency of 50 Hz (Monache et al., "Inhibition of Angiogenesis
Mediate by
Extremely Low-Frequency Magnetic Fields (ELF-MFs)," PLOS One, 8:11 (Nov 2013).
Different types of cells, including without limitation different types of
cancer cells, may
require different frequencies for interruption of angiogenesis.
[0043]Accordingly, in one embodiment an MFT therapy having a bimodal magnetic
field
frequency distribution may be applied to the target body area. In one
exemplary
embodiment, the APMFT 110 may generate a first electrical signal to cause a
first AP
electromagnetic coil 120 to generate a first variable AP magnetic field
distribution that
varies the magnetic field frequency over a first time period (e.g., 1 second,
1 minute, 10
minutes, 1 hr) between a first lower limit (e.g., 0.5 kHz) and a first upper
limit (e.g., 5 kHz)
to broadly interrupt a first metabolic process (e.g., angiogenesis) a target
cell population,
as defined by frequency control module 114. The APMFT 110 may also generate a
second electrical signal to cause the same or a second AP electromagnetic coil
120 to
generate a second variable AP magnetic field distribution that varies the
magnetic field
frequency over a second time period (e.g., 1 second, 1 minute, 10 minutes, 1
hr) between
a second lower limit (e.g., 50 kHz and a second upper limit (e.g., 400 kHz) to
broadly
interrupt a second metabolic process (e.g., the mitosis cycle) of rapidly-
dividing cells.
Additional coils may produce different fixed or variable-frequency AP magnetic
fields
having different frequencies or frequency ranges to interrupt still other
aspects of the
reproduction cycle of rapidly-dividing cells. In an alternative example, a
single AP
electromagnetic coil 120 may be used to sequentially deliver AP magnetic
fields within
two different AP frequency ranges (e.g., 1 ¨ 5 kHz for a first treatment
period, followed by
50 ¨ 400 kHz for a second treatment period).
[0044] In variable-frequency embodiments, many different ways of implementing
a
changing frequency are possible, and enumeration herein of specific
embodiments of
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varying frequencies is illustrative and is not intended to be limiting. It
will be appreciated
that additional variable-frequency embodiments may be implemented in view of
the
present disclosure. In one embodiment, a magnetic field may be generated
having a
single frequency that varies from a lower frequency (e.g., 50 kHz) to an upper
frequency
(e.g., 250 kHz) in a uniform manner (i.e., non-varying rate of frequency
change) within a
defined frequency range time period or at a desired (e.g., programmed)
frequency change
rate. In another embodiment, the frequency may vary in a non-uniform manner
such as
stepwise changes in frequency or different ranges of change (e.g., rates of
change of
frequency are highest near the mid-point between the upper and lower frequency
limits).
In a still further embodiment, the frequency may vary continuously or
intermittently, with
variable-frequency periods alternating with non-variable frequency periods. In
additional
embodiments, a field having two different frequencies may simultaneously be
applied to
the target body area (emitted, e.g., by a single coil or by two different
coils). By providing
multiple (e.g., 2 or more) coils, MFT therapies having a desired frequency
distribution
(e.g., random, Gaussian, or non-Gaussian) either sequentially or
simultaneously may be
applied to one or more target areas.
[0045] The electrical signal from APMFG 110 to AP electromagnetic coils 120
also defines
the field strength of the AP magnetic fields produced by the coils, as defined
by magnetic
field strength control module 116. MFT therapy systems 100 of the present
invention may
use relatively low magnetic field strengths to destroy or impair rapidly-
proliferating cells.
Preferably, MFT therapy fields in systems 100 of the present invention have
field
strengths of less than 5 milliTesla (i.e., 5,000 pT), such as field strengths
within the range
of 0.05 - 5 mT. In a preferred embodiment, the field strengths are within the
range of 0.2
- 2 mT, and more preferably within the range of 0.5 - 1.2 mT.
[0046] In one embodiment, the magnetic field may have a single, non-varying
field
strength. Without being bound by theory, it is believed that different cell
sizes (e.g.,
different types of cancers) may require different field strengths for maximum
efficacy in
destroying or inhibiting cell division. Within such embodiments, however, the
AP magnetic
fields may have a single, non-varying field strength either continuously or
intermittently
according to a defined duty cycle as defined by, e.g., timing control module
112 and
magnetic field strength control module 116.
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[0047] In variable-field-strength embodiments, many different ways of varying
the field
strength can be envisioned, similar to the variations described above
respecting
frequency changes. As with frequency, enumeration herein of specific
embodiments of
varying field strength is illustrative, not limiting. Additional variable-
field-strength
embodiments may be implemented (e.g., by magnetic field strength control
module 116)
in view of this disclosure. In one embodiment, a magnetic field may have a
field strength
that varies from a lower limit (e.g., 0.05 mT) to an upper limit (e.g., 1 mT)
in a uniform
manner (i.e., with a non-varying rate of change) within a defined field
strength range time
period. In another embodiment, the field strength may vary in a non-uniform
manner such
as stepwise changes in field strength or with a swept field strength variation
with
accelerating or decelerating field strength variation (e.g., rates of change
of field strength
are highest near the upper and lower limits of the field strength range). In a
still further
embodiment, magnetic field strength may vary continuously or intermittently,
with
variable-field-strength periods alternating with non-variable-field-strength
periods. In
some embodiments, AP magnetic fields at two different frequencies, each having
a
different field strength, may simultaneously be applied to the target body
area (emitted,
e.g., by two different AP electromagnetic coils 120).
By providing multiple AP
electromagnetic coils 120, MFT therapies having a desired frequency and
magnetic field
strength distribution (e.g., random, Gaussian, or non-Gaussian), either
sequentially or
simultaneously may be applied to the target body area.
[0048] Because MFT therapies act only on dividing cells, overall efficacy
corresponds to
lengthy treatment periods (e.g., many hours or days, and in some cases weeks.
However,
to minimize damage to normal (e.g., non-cancerous or non-tumor) cells, in some
embodiments the therapy is suspended for certain periods. This may involve,
for example,
providing MFT therapy continuously with defined alternating on-time (e.g., a
time period
withing a range of 1 sec ¨ 24 hr) and off-time (e.g., 1 sec ¨ 24 hr) periods
according to a
defined treatment duty cycle as defined by timing control module 112.
In one
embodiment, the on-time and off-time periods may be a time period within a
range of 1
second ¨ 1 week, 1 sec ¨ 24 hr, 1 minute ¨ 12 hr, etc.). In one such exemplary
embodiment, the MFT therapy is provided continuously at a 10:1 duty cycle by
generating
and applying the MFT therapy fields for ten (10) minutes, followed by 1 minute
in which
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no therapy is applied, with the process repeated until a predefined total
treatment duration
(e.g., 2 weeks) is complete. In another embodiment, the same 10:1 duty cycle
may be
administered by applying the MFT therapy fields for ten hours, followed by a
one-hour
suspension of therapy, and repeating the process until the total treatment
period is
complete.
[0049] In another embodiment, MFT therapy according to a defined treatment
duty cycle
comprising on-time and off-time periods may be administered for a defined
treatment
duration (e.g., 1 hr, 6 hr, 8 hr, 24 hr) after which no further treatment is
applied. In a still
further embodiment, the MFT therapy may be administered according to the
patient's
circadian rhythms (e.g., continuously at night or when the patient is
sleeping, and
according to a defined duty cycle for defined periods during the day such as
morning
hours, afternoon hours, or evening hours). It will be appreciated that other
duty cycles
and treatment durations may be used, and that the therapy may involve, as
previously
discussed, constant or variable magnetic field frequencies and field
strengths.
[0050] In another embodiment, MFT therapy may be applied according to a
defined
treatment duty cycle of on-time and off-time periods, with the magnetic field
strength
varying according to a defined field strength duty cycle. This may involve,
for example, a
10:1 treatment duty cycle combined with a 4:1 field strength duty cycle. As a
specific
example, the MFT therapy may be provided for a 24 hr treatment duration, at a
10:1
treatment duty cycle with AP magnetic fields applied to a target body area for
10 minutes,
followed by 1 minute in which no AP magnetic fields are applied. Within the 10
minute
treatment periods, 8 minutes may involve variable frequency treatment within a
first field
strength range of 3.0 ¨ 4.0 mT, followed by 2 minutes of treatment within a
second field
strength range of 0.5 ¨ 1.5 mT, providing a 4:1 field strength duty cycle.
[0051] In alternative embodiments, MFT therapy fields may be applied according
to the
patient's circadian rhythms, or according to specific times of day. For
example, the MFT
therapy fields may be applied to the target body area only during daytime
hours; only
during nighttime hours; during all daytime hours except during mealtime hours;
during all
daytime hours except when the patient is exercising (as detected by, e.g., an
activity
monitor); during specific hours of the day (e.g., 9:00AM-noon and 6:00PM-
5:00AM).
These examples are intended to be exemplary only, and it will readily be
appreciated that
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delivery of MFT therapy fields can be tailored to suspend therapy during
certain hours
that would be most convenient to the patient, while also minimizing damage to
normal
(i.e., non-rapidly-dividing) cells.
[0052] Most magnetic field-generating coils are constructed so as to generate
a magnetic
field having an axis along which the magnetic field lines are directed. In
some
embodiments, multiple AP magnetic coils 120 can be spatially aligned in such a
manner
that a desired magnetic field distribution is generated in area of interest,
such as the
entirety or a portion of the target body area.
[0053] In some embodiments, one or more parameters defining the MFTT therapy
(e.g.,
frequency, field strength, selection of specific coils among a plurality of
available coils)
may be determined based on the results of certain tests. For example, an
imaging
procedure may be performed to identify the type and location of the target
rapidly-dividing
cells (e.g., cancer or tumor cells). In various embodiments, the imaging
procedure may
be an imaging procedure using one or more of an MRI system, a CT scan system,
a PET
scan system, and an X-ray system.
[0054] Based on the results of the imaging (e.g., cell size(s), type of cells,
location of cells,
etc.) a healthcare provider such as a physician may select one or more
parameters of the
MFT therapy, including without limitation, the frequency/frequencies of the
magnetic
field(s), the field strength(s), the positioning of one or more coils, a coil
size, a type of
retaining element (e.g., a garment type) to maintain the coils in position
relative to the
target body area, a duty cycle or schedule for applying therapy, etc. It will
be appreciated
that the foregoing and other parameters may also be selected based on other
tests, e.g.,
a pathological analysis of the cancer cells such as a microscopic analysis of
a biopsy, a
chemical test, a genetic test, etc.
[0055] In some instances, the results of an imaging procedure prior to the
MFTT therapy
may identify a target body area to which MFTT therapy is to be directed. Based
on the
location of the target body area, in some embodiments a retaining element may
be
necessary to retain the magnetic coils in a desired position relative to the
target treatment
area or tissue. Various retaining elements may be used to unobtrusively and
securely
maintain the magnetic coils in a desired position relative to a desired target
area of the
patient's body. For example, a bra may be used to house the magnetic coils for
treatment
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of breast cancer cells. In another example, a hat may be used to retain
magnetic coils in
position to treat brain cancer. In still another example, a neck cuff, collar,
or scarf may
retain one or more magnetic coils for treatment of esophageal cancer, and a
shirt may be
used to retain one or more magnetic coils to treat lung cancer. In another
embodiment,
the retaining element may be a bandage such as an adhesive bandage capable of
adhering to the target body area or to skin adjacent thereto. These examples
are
exemplary and not limiting, and it will be appreciated that a variety of other
or additional
retaining elements may be used depending upon the target tissue location.
Because the
magnetic coils do not need to be in direct contact with the skin of the
patent, the retaining
elements may include pouches or pockets for securely retaining the coils in
position with
a comfortable and biocompatible lining placed between the coil and the skin or
target
treatment area. In some embodiments, the AP electromagnetic coils 120 are
completely
integrated within the retaining element during manufacturing (e.g., the coils
are
completely integrated inside a garment such as a bra, hat, shirt, bandage,
etc.) In various
embodiments, the retaining element may include a lead wire for coupling each
of the one
or more coils 120 to the AP magnetic field generator 110 and/or controller. In
alternative
embodiments, a direct electrical coupling (e.g., a snap fit) may be used
between an
electronics package and the AP electromagnetic coil(s) 120. The electronics
package
may include one or more of the power supply 150, controller 130, APMFG 110,
and
interface 140.
[0056] Figure 2 illustrates a bra 200 that acts as a retaining element for one
or more
magnetic coils 220 for applying one or more magnetic fields to a target body
area to treat
cancer cells or other rapidly-dividing cells in breast tissue. Magnetic coils
220 may be the
same as coils 120 described in Figure 1, but may be adapted for placement in
bra 200
(e.g., with a size, geometry, etc., for treatment of breast tissue). Bra 200
may in many
aspects be constructed similarly to existing bras available at retail clothing
outlets, and
may include cups 210 for holding breast tissue and retaining coils 220 in
position relative
to a target body area comprising breast tissue. Straps 230 may be provided to
secure
the bra 200 to the shoulders of the patient, and side straps or bands 240 for
securing the
bra to the patient's torso. AP electromagnetic coils 220 may be integrated
into bra 200,
or may be removably coupled thereto.
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[0057] One or more cables or wires 250 may be provided to couple each of the
coils 220
to an electronics box 260, which may house the remaining components of the MFT
therapy system 100 of Figure 1 such as APMFG 110, controller 130, power supply
150,
and in some embodiments interface 140. In alternative embodiments, one or more
of the
APMFG 110, controller 130, power supply 150, or interface 140 may be provided
separately from the electronics box 260. For example, interface 140 may
comprise a
mobile phone app that communicates directly with one or more of APMFG 110,
controller
130, power supply 150, etc., as well as receiving and displaying information
from one or
more of the foregoing system components. The mobile phone app interface may
allow
the patient or a healthcare provider to program one or more treatment
parameters for the
MFT therapy system 100, and may display information relating to the MFT
therapy or
system 100 status (e.g., displaying how long the MFT therapy has been applied,
whether
a magnetic field is currently being applied to the target tissue from each of
the coils 220,
the frequency and/or field strength of the currently-provided magnetic fields,
remaining
battery life, etc.).
[0058] Figure 3 illustrates a hat 300 that acts as a retaining element for one
or more AP
electromagnetic coils 320 for applying one or more magnetic fields to the
treatment of
cancer or other rapidly-dividing cells in a target body area comprising brain
tissue.
Magnetic coils 320 are, in one embodiment, similar to AP electromagnetic coils
120
described in Figure 1, but may be adapted for placement in hat 300. This may
include
changes in the size, geometry, or other characteristics to enable effective
placement in
hat 300 for treatment of brain tissue. Although depicted as a baseball cap, it
will be
apparent that many other hat types and styles may be used for hat 300 (e.g.,
skullcap,
beret, fedora, etc.). In one embodiment, hat 300 may be a skullcap of an
appropriate size
to fit closely on the head of the patient, and the magnetic coils 320 may be
have a concave
shape adapted for location or placement in the cap, e.g., inside the hat or in
a pocket
between an inner and outer layer thereof. AP electromagnetic coils 320 may be
integrated into hat 300, or may be removably coupled thereto.
[0059] One or more cables or wires 350 may be provided to couple each of the
AP coils
320 to an electronics box 360, which may house the remaining components of the
MFT
therapy system 100 of Figure 1 such as APMFG 110, controller 130, power supply
150,
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and in some embodiments interface 140. In alternative embodiments, one or more
of the
APMFG 110, controller 130, power supply 150, or interface 140 may be provided
separately from the electronics box 360. For example, as described in
connection with
Figure 2, a separate interface 140 may be provided as a mobile phone app that
communicates directly with one or more of APMFG 110, controller 130, power
supply
150, etc. Such an app-based interface may also provide information on the MFT
therapy
to the patient or a healthcare provider (e.g., displaying how long the MFT
therapy has
been applied, whether a magnetic field is currently being applied to the
target tissue from
each of the coils 320, the frequency and/or field strength of the currently-
provided
magnetic fields, remaining battery life, etc.).
[0060] Figure 4 illustrates a shirt 400 that acts as a retaining element for
one or more AP
electromagnetic coils 420 for applying one or more magnetic fields to the
treatment of
cancer or other rapidly-dividing cells in a target tissue in a patient's
thoracic or abdominal
region. This may include, without limitation and depending on the placement of
the one
or more AP electromagnetic coils 420, treatment of lung cancer, liver cancer,
pancreatic
cancer, or cancers or tumors in other thoracic or abdominal organs or
structures. AP
electromagnetic coils 420 are, in one embodiment, similar to coils 120
described in Figure
1, but may be adapted for placement in shirt 400 based on the target tissue.
This may
include changes in the coil size, geometry, or other characteristics to enable
effective
placement in shirt 400 and for treatment of the particular target tissue.
Although depicted
as a T-shirt, that many other types and styles of shirt may be used as shirt
400, including
long-sleeve or short sleeve shirts; button, zip, or pullover shirts. In
addition, it will be
understood that shirt 400 may comprise other garments that may cover the
thoracic or
abdominal region of a patient, including sweaters, jackets, coats, etc.,
although in
preferred embodiments a shirt that fits tightly to the patient's body is used
to better retain
the AP electromagnetic coils 420 in a more precise or controlled placement
relative to the
target tissue. AP electromagnetic coils 420 may be adapted for location or
placement on
the inside, outside or in a pocket of shirt 400, and may be integrated into or
removably
coupled thereto.
[0061] One or more cables or wires 450 may be provided to couple each of the
coils 420
to an electronics box 460, which may house the remaining components of the MFT
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therapy system 100 of Figure 1 such as APMFG 110, controller 130, power supply
150,
and in some embodiments interface 140. In alternative embodiments, one or more
of the
APMFG 110, controller 130, power supply 150, or interface 140 may be provided
separately from the electronics box 460. For example, a separate interface 140
may be
provided as a mobile phone app that communicates with one or more of APMFG
110,
controller 130, power supply 150, etc. Such an app-based interface may also
provide
information on the treatment therapy to the patient or a healthcare provider
(e.g.,
displaying how long the therapy has been applied, whether a magnetic field is
currently
being applied to the target tissue from each of the coils 420, the frequency
and/or field
strength of the currently-provided magnetic fields, remaining battery life,
etc.).
[0062] Figure 5 illustrates a neck cuff or collar 500 that acts as a retaining
element for one
or more AP electromagnetic coils 520 for applying one or more magnetic fields
to the
treatment of cancer or other rapidly-dividing cells in a target tissue in a
patient's neck
area, including without limitation esophageal cancer, laryngeal cancer, etc.
AP
electromagnetic coils 520 may be similar to coils 120 described in Figure 1,
but may be
adapted for placement in neck cuff or collar 500 based on the target treatment
area or
tissue. This may include changes in the size, geometry, or other
characteristics to enable
effective placement in neck cuff 500 and for treatment of the particular
target tissue. Neck
cuff or collar 500 preferably includes a securing and/or adjustment tab 530
(e.g., Velcro)
to adjust the cuff or collar to the patient's size and to secure it in a fixed
position relative
to the patient's neck. In one alternative embodiment, a neck scarf may be used
as a
retaining element. AP electromagnetic coils 520 may be adapted for location or
placement on the inside, outside or in a pocket of neck cuff or collar 500,
and may be
integrated into or removably coupled thereto.
[0063] One or more cables or wires 550 may be provided to couple each of the
coils 520
to an electronics box 560, which may house the remaining components of the MFT
therapy system 100 of Figure 1 such as APMFG 110, controller 130, power supply
150,
and in some embodiments interface 140. In alternative embodiments, one or more
of the
APMFG 110, controller 130, power supply 150, or interface 140 may be provided
separately from the electronics box 560. For example, a separate interface may
be
provided as a mobile phone app that communicates with one or more of APMFG
110,
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controller 130, power supply 150, etc. Such an app-based interface may also
provide
information on the treatment therapy to the patient or a healthcare provider
(e.g.,
displaying how long the therapy has been applied, whether a magnetic field is
currently
being applied to the target tissue from each of the coils 520, the frequency
and/or field
strength of the currently-provided magnetic fields, remaining battery life,
etc.).
[0064] Figure 6 illustrates a bandage 600 that acts as a retaining element for
one or more
magnetic coils 620 for applying one or more magnetic fields to the treatment
of cancer or
other rapidly-dividing cells in a target tissue anywhere on the body. Magnetic
coils 620
may be similar to those described in Figure 1, but may be adapted for
placement in
bandage 600 based on the target tissue. This may include changes in the size,
geometry,
or other characteristics to enable effective placement in bandage 600 and for
treatment
of any of a variety of different target tissues. Magnetic coils 620 may be
adapted for
location or placement on the inside, outside or in a pocket of bandage 600,
and may be
integrated into or removably coupled thereto.
[0065] One or more cables or wires 650 may be provided to couple each of the
coils 620
to an electronics box 660, which may house the remaining components of the MFT
therapy system 100 of Figure 1 such as APMFG 110, controller 130, power supply
150,
and in some embodiments interface 140. In alternative embodiments, one or more
of the
APMFG 110, controller 130, power supply 150, or interface 140 may be provided
separately from the electronics box 560. For example, a separate interface may
be
provided as a mobile phone app that communicates with one or more of APMFG
110,
controller 130, power supply 150, etc. Such an app-based interface may also
provide
information on the treatment therapy to the patient or a healthcare provider
(e.g.,
displaying how long the therapy has been applied, whether a magnetic field is
currently
being applied to the target tissue from each of the coils 620, the frequency
and/or field
strength of the currently-provided magnetic fields, remaining battery life,
etc.).
[0066] Certain embodiments of the retaining element may also provide
additional features
to enable the MFT therapy to be conveniently delivered to the target body area
or tissue.
In one embodiment, the retaining element may have integrated magnetic coils
120,
APMFG 110, and controller 130, either as separate items in the retaining
element or as
a single unit. A wire (not shown) may be provided to couple the power supply
to one or
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more of the APMFG 110, coils 120, controller 130, and interface 140. In one
embodiment,
the power supply 150 provides power to the controller, which includes
circuitry (e.g.,
rectifiers, converters, transformers, etc.) to modify the electrical power
received from the
power supply to provide electrical power to controller 130, which in turn
distributes power
to the APMFG 110, AP electromagnetic coils 120, and interface 140. In this
embodiment,
a power supply (e.g., a battery) may be located elsewhere in close proximity
to the patient
(e.g., in a pocket in the patient's trousers or a jacket).
[0067] In some embodiments, the MFT therapy may be provided to a patient in
combination with one or more other therapies such as an anti-cancer drug,
radiation
therapy, or TTF therapy (e.g., therapy is described in US 6,868,289 or US
8,019,414).
The MFT therapy system 100 preferably permits the other (i.e., non-MFT)
therapy to be
provided at a lower dosage than would be administered in the absence of the
MFT therapy
to the target body area or tissue, or at a reduced frequency than would be
administered
in the absence of the MFT therapy, or both. In various embodiments, the co-
therapy
applied with the MFT therapy may be a drug selected from a chemotherapy drug,
a
hormone receptor drug, targeted therapy drugs, immunotherapy, angiogenesis
inhibitor
drugs, a checkpoint inhibitor drug, and a HER2 receptor drug. In other
embodiments the
co-therapy may be a radiation therapy selected from an internal radiation
therapy and an
external beam radiation therapy. In still other embodiments, the co-therapy
applied with
the MFT therapy may be a TFT therapy involving the application of electrical
fields to the
target tissue. Without being bound by theory, it is anticipated that one or
more co-
therapies (or adjuvant therapies), when combined with MFT therapy, may achieve
superior results that either therapy when administered alone. In various
embodiment the
combination therapy may comprise administering MFT therapy with an anti-cancer
drug,
radiation, or TTF therapy either simultaneously or sequentially.
[0068] It may be desirable in some instances to shield non-target body areas
from the
MFT therapy fields. In such instances an optional magnetic field shield (not
shown) may
be provided to shield the non-target areas from the effects of the magnetic
fields. In some
embodiments, highly localized shields may be provided to shield specific
structures within
the target body area of the patient, such as specific blood vessels or organ
structures that
are adjacent to the target rapidly-dividing cells.
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[0069] It is known that electric fields induce magnetic fields and vice versa.
However,
without being bound by theory, the present invention involving MFT therapy
appears to
provide a therapy having a different mode of action than prior art TTF and/or
drug
therapies. In particular, TTF therapies use capacitive electrodes to induce
primarily
electric fields at relatively high electric field strengths. According to
reported literature
(e.g., Kirson et al., Cancer Research 2004) TTF therapies begin to inhibit
tumor cell
growth at a field strength of about 100 V/m at frequencies of 50 ¨ 250 kHz. In
one recent
experiment (see Experiment 1 below), MFT therapies showed surprising results
with a
similar inhibition of tumor cell growth as reported for TTF therapies but at a
fraction (e.g.,
less than 3%) of typical TTF therapy electric field strengths.
[0070] EXPERIMENT 1
[0071] Mouse melanoma cells (B16F10 cell line, obtained from the University of
California-Berkeley) were incubated in Dulbecco's Modified Eagle Medium (DMEM)
in 36
middle wells (5.0 mm diameter) of a 96 well plate for 24 hours at 37 C. The
cells in each
of the 36 treatment wells were then exposed for 24 hours to an alternating
magnetic field
at a frequency of 150 kHz and a magnetic field strength of approximately 0.8
mT using a
Helmholtz coil, maintained at a temperature of 37 C. Control wells were not
exposed to
the alternating magnetic field and were incubated at 37 C for the same time
period. After
24 hours, the alternating magnetic field was discontinued and histology was
performed
for cells in each well (both treatment and control). Figures 7A and 7B are
illustrative of
the differences between typical control and treatment wells. Controls
exhibited a
significantly higher cell count per well as shown by gross comparison. In
addition, control
cells maintained a typically angular morphological structure as indicating in
Figure 7A.
Magnetic field-treated cells showed significantly decreased cell count and in
addition
demonstrated rounded morphology indicating cell stress, as shown in Figure 7B.
[0072] Figure 8 provides a bar chart comparison summarizing the results of
treatments
performed on two different places with 36 wells in each plate. Normalizing the
cell counts
of the control wells as 100, the treated cells shown a reduction of
approximately 31%.
Although treatment by magnetic fields and electrical fields (e.g., TTF
therapy) are
fundamentally different (e.g., using coils vs electrodes and generating
primarily magnetic
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vs. electric fields), it is possible to calculate the strength of the induced
electric field from
the coils used in Experiment 1 using the equation
r dB
Eõ = --
- 2 dt
[0073] Using equation 1 yields a maximum inducted voltage of 2.34 V/m, or less
than 3%
of the electric field strengths reported as required for inhibitory activity
in TTF therapy.
Because Experiment 1 indicates that MFT therapy exhibits effects on cancer
cells at such
a small fraction of the electrical field strength of TTF therapy, it enables
therapies having
significant advantages over TTF therapies, including without limitation
ambulatory
therapies that allow patients to continue many ordinary day-to-day activities
with without
interruption, and minimal encumbrance or burden.
[0074] Part of the advantage of MFT therapies over TTF therapies stem from the
different
hardware configuration of the two systems. While TTF therapies use insulated
(e.g.,
ceramic coated) electrodes, the use of coils instead of electrodes in MFT
therapy confers
a number of benefits. Because MTF therapy coils¨in contrast to the insulated
electrodes
of TTF therapies¨do not need to be in direct contact with the body, MFT coils
can be
separated from target issue by one or more clothing layers (e.g., a garment or
undergarment). By applying magnetic fields through clothing, MFT therapies
provide
increased patient comfort and a less cumbersome patient experience.
[0075] In addition, MFT therapies can be implemented with significantly less
risk to the
patient that TTF therapies involving electrodes. The use of coils instead of
electrodes
results in only a de minim is induced electrical current during MFT therapies,
and thus the
risk of electrical shorting and consequent uncontrolled hearing of patient
body tissue is
negligible.
[0076] Furthermore, because MFT therapies involve coils that can be made
relatively
small and with no current flow through the patient's body, systems for MTF
therapies can
allow long treatment periods to target cancer and other hyperproliferating
cells with little
inconvenience to the patient. These and other advantages of MTF therapies over
TTF
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therapies will be more fully appreciated by persons of skill in the art in
view of the present
disclosure.
[0077] In various embodiments, the present invention relates to the subject
matter of the
following numbered paragraphs.
[0078] 101. A method of treating cancer cells in a target body area of a
patient,
comprising:
coupling an AP electromagnetic coil to the target body area; and
applying an alternating polarity (AP) magnetic field to the target body area
using
the AP electromagnetic coil, the AP magnetic field having a frequency of 0.5 -
500 kHz
and a field strength of 0.05 - 5 mT, wherein the AP magnetic field selectively
affects the
cancer cells to achieve at least one of damaging the cancer cells, inhibiting
the growth of
the cancer cells, reducing tumor size, inhibiting angiogenesis, or preventing
metastasis
of the cancer cells, while leaving non-cancer cells substantially unharmed.
[0079] 102. The method of claim 101, further comprising:
coupling a controller to the AP electromagnetic coil, wherein the controller
controls
the frequency and field strength of the AP magnetic field.
[0080] 103. The method of claim 101, wherein applying an AP magnetic
field
comprises applying an AP magnetic field having a frequency of 25 ¨ 400 kHz and
a field
strength of 0.2 ¨ 2 mT.
[0081] 104. The method of claim 101, wherein applying an AP magnetic
field
comprises applying an AP magnetic field having a frequency of 100¨ 300 kHz and
a field
strength of 0.5 ¨ 1.2 mT.
[0082] 201. A method of treating cancer cells in a target body area of a
patient,
comprising:
providing at least one electromagnetic coil;
providing a controller coupled to the at least one electromagnetic coil;
coupling the at least one electromagnetic coil to the target body area;
applying to the target body area an alternating polarity (AP) magnetic field
having
a frequency of 0.5 - 500 kHz and a field strength of 0.05 - 5 mT, wherein the
AP magnetic
field is generated by the at least one electromagnetic coil under the control
of the
controller, and the AP magnetic field selectively affects the cancer cells to
achieve at least
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one of damaging the cancer cells, inhibiting the growth of the cancer cells,
reducing tumor
size, inhibiting angiogenesis, or preventing metastasis of the cancer cells,
while leaving
non-cancer cells substantially unharmed.
[0083] 202. The method of claim 201, wherein applying an AP magnetic
field
comprises applying an AP magnetic field having a frequency of 25 ¨ 400 kHz and
a field
strength of 0.2 ¨ 2 mT.
[0084] 203. The method of claim 201, wherein applying an AP magnetic
field
comprises applying an AP magnetic field having a frequency of 100¨ 300 kHz and
a field
strength of 0.5 ¨ 1.2 mT.
[0085] 204. The method of claim 201, wherein applying an AP magnetic
field
comprises applying the AP electrical field to the target body area according
to at least
one of a treatment duty cycle and a field strength duty cycle.
[0086] 205. The method of claim 204, wherein the treatment duty cycle
comprises
alternating periods of an on-time in which the AP magnetic field is applied to
the target
tissue, and an off-time in which the AP magnetic field is not applied to the
target tissue.
[0087] 206. The method of claim 204, wherein the field strength duty
cycle
comprises alternating periods in which the AP magnetic field is applied to the
target tissue
for a first time period at a first field strength followed by a second time
period at a second
field strength.
[0088] 207. The method of claim 201, wherein the AP magnetic field
comprises a
bimodal magnetic field frequency distribution comprising a first variable AP
magnetic field
that varies the magnetic field frequency between a first lower limit and a
first upper limit
and a second variable AP magnetic field that varies the magnetic field
frequency between
a second lower limit and a second upper limit.
[0089] 208. The method of claim 201, wherein the AP magnetic field
comprises at
least one of a variable frequency and a variable field strength.
[0090] 209. The method of claim 1, further comprising administering to
the patient
at least one additional anti-cancer therapy selected from an anti-cancer drug,
a radiation
therapy, and TTF therapy.
[0091] 210. The method of claim 209, wherein administering a TTF therapy
comprises applying at least one AC electrical field to the target tissue,
wherein the AC
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electrical field comprises a frequency of 50-500 kHz and an electric field
strength of about
10- 1000 V/m.
[0092] 301. A system for treating cancer cells in a target body area of a
patient
comprising:
at least one electromagnetic coil coupled to a target body area; and
a controller for controlling the at least one electromagnetic coil to generate
and
apply to the target body area an AP magnetic field having a frequency of 0.5 -
500 kHz
and a field strength of 0.05-5 mT, wherein the AP magnetic field selectively
affects the
cancer cells to achieve at least one of damaging the cancer cells, inhibiting
the growth of
the cancer cells, reducing tumor size, inhibiting angiogenesis, or preventing
metastasis
of the cancer cells, while leaving non-cancer cells substantially unharmed.
[0093] 302. The system of claim 301, wherein the cancer cells are one of
breast
cancer cells, lung cancer cells, lung carcinoid tumor cells, thymic cancer
cells, tracheal
cancer cells, pancreatic cancer cells, liver cancer cells, stomach cancer
cells, kidney
cancer cells, ovarian cancer cells, colon cancer cells, rectal cancer cells,
prostate cancer
cells, throat cancer cells, thyroid cancer cells, mouth cancer cells, nose
cancer cells, and
salivary gland cancer cells.
[0094] 303. The system of claim 302 wherein the at least one
electromagnetic coil
is coupled to the target body area by a retaining element during the
application of the AP
magnetic field to the target body area.
[0095] 304. The system of claim 303, wherein the cancer cells are breast
cancer
cells, and the retaining element is a wearable garment selected from a bra, a
shirt, and a
vest.
[0096] 305. The system of claim 303, wherein the cancer cells are
selected from
lung cancer, lung carcinoid tumors, thymic malignancies, tracheal tumors,
pancreatic
cancer, liver cancer, stomach cancer, kidney cancer, ovarian cancer, colon
cancer and
rectal cancer, and the retaining element is a wearable garment selected from a
bra, a
shirt, a vest, and a jacket.
[0097] 306. The system of claim 303, wherein the cancer cells are lower-body
cancer
cells selected from prostate cancer cells, ovarian cancer cells, colon cancer
cells, and
rectal cancer cells, and the retaining element is an undergarment.
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[0098] 307. The system of claim 303, wherein the cancer cells
[0099] 308. The system of claim 301 wherein the at least one
electromagnetic coil
is coupled to the target body area by a retaining element during the
application of the AP
magnetic field to the target body area
[0100] 309. The system of claim 308 wherein the retaining element is
selected
from a bra, a shirt, a vest, a jacket, an undergarment, and a bandage.
[0101] 310. The system of claim 301, wherein the at least one
electromagnetic
coil comprises a plurality of electromagnetic coils coupled to the target body
area to obtain
a desired magnetic field distribution in the target body area.
[0102] 311. The system of claim 301, further comprising:
an electromagnetic shield for shielding at least one non-target body area of
the patient's
body from exposure to the AP magnetic field.
[0103] 401. A system for treating cancer cells in a target area of a
patient's body
comprising:
at least one electromagnetic coil coupled to a target body area; and
a controller for controlling the at least one electromagnetic coil to generate
and
apply to the target body area an alternating polarity (AP) magnetic field
having a
frequency of 5 Hz - 500 kHz and a field strength of 0.05 - 5 mT, wherein the
AP magnetic
field selectively affects the cancer cells to achieve at least one of damaging
the cancer
cells, inhibiting the growth of the cancer cells, reducing tumor size,
inhibiting
angiogenesis, or preventing metastasis of the cancer cells, while leaving non-
cancer cells
substantially unharmed.
[0104] 402. The system of claim 401, further comprising:
a power supply for supplying power to said electromagnetic coil.
[0105] The particular embodiments disclosed above are illustrative only, as
the invention
may be modified and practiced in different but equivalent manners apparent to
those
skilled in the art having the benefit of the teachings herein. Embodiments of
the present
invention disclosed and claimed herein may be made and executed without undue
experimentation with the benefit of the present disclosure. While the
invention has been
described in terms of particular embodiments, it will be apparent to those of
skill in the art
that variations may be applied to systems and apparatus described herein
without
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departing from the concept, spirit and scope of the invention. Examples are
all intended
to be non-limiting. It is therefore evident that the particular embodiments
disclosed above
may be altered or modified and all such variations are considered within the
scope and
spirit of the invention, which are limited only by the scope of the claims.
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