Novocure Gmbh

Leland Stanford Junior University

Other

Tali Voloshin-Sela

Hadas Sara Hershkovich

Moshe Giladi

Eilon Kirson

Lilach Avigdor

Malgorzata Burek

Mario Lohr

Carola Forster

Catherine Brami

Carsten Hagemann

Almuth F Kessler

Yoram Wasserman

Zeev Bomzon

Ariel Naveh

Golan Bar-Tal

Ze'ev Bomzon

Sanjiv Sam Gambhir

Reuven Ruby Shamir

Noa S Kaynan

Edwin Chang

Chirag B Patel

Yaara Porat

Yoram Palti

Shiri Davidi

Uri Weinberg

Einav Zeevi

Ze′ev Bomzon

Rosa S Schnaiderman

Adrian Kinzel

Yaniv Alon

Hadas Hershkovish

Boris Brant

Karnit Gotlib

Stuart Smith

A computer-implemented method to determine placement of transducers on a subject's body for applying tumor treating fields, the method including: determining a pair of locations on the subject's body for placement of a pair of transducer arrays based on image data; receiving a detected concentration of a target molecule within a target region of the subject's body from a molecular imaging apparatus, the concentration of the target molecule being detected after tumor treating fields are induced between the pair of transducer arrays; determining, based on the detected concentration of the target molecule, how the tumor treating fields were distributed in the target region; determining a recommendation of a second pair of locations on the subject's body for placement of the pair of transducer arrays based on the distribution of the tumor treating fields in the target region; and outputting the recommendation of the second pair of locations to a user.

Adjusting tumor treating fields simulation and treatment using molecular imaging

Disclosed are methods of imaging a cancer cell, the method comprising applying a first alternating electric field at a first frequency to the cancer cell for a first period of time, wherein application of the first alternating electric field at the first frequency to the cancer cell for the first period of time increases permeability of cell membranes of the cancer cell; introducing a nanoparticle to the cancer cell, wherein the increased permeability of the cell membranes enables the nanoparticle to cross the cancer cell membrane; and imaging the cancer cell.

Compositions and methods for imaging a cell

Methods of treating diseases and infections by applying alternating electric fields to tissues followed by administering a treatment for the disease or infection are provided. In some instances, alternating electric fields can be applied at least until substantial improvement in disease manifestation. The exemplary methods can be used to treat kidney, heart, brain, and bone disease and conditions.

Methods of treating disease by skewing macrophage phenotype with alternating electric fields

Disclosed are methods of altering the electric impedance to an alternating electric field in a target site of a subject, comprising introducing a nanoparticle to a target site in the subject; and applying an alternating electric field to the target site of the subject, wherein the electric impedance in the target site of the subject to the alternating current is altered. Disclosed are methods for improving transport of a nanoparticle across a cell membrane of a cell, the method comprising applying an alternating electric field to the cell for a period of time, wherein application of the alternating electric field increases permeability of the cell membrane; and introducing the nanoparticle to the cell, wherein the increased permeability of the cell membrane enables the nanoparticle to cross the cell membrane. Disclosed are methods of imaging a cancer cell, the method comprising applying a first alternating electric field at a first frequency to the cancer cell for a first period of time, wherein application of the first alternating electric field at the first frequency to the cancer cell for the first period of time increases permeability of cell membranes of the cancer cell; introducing a nanoparticle to the cancer cell, wherein the increased permeability of the cell membranes enables the nanoparticle to cross the cancer cell membrane; and imaging the cancer cell.

Compositions and methods of altering the electric impedance to an alternating electric field

Disclosed herein are methods of increasing sensitivity of a cancer cell to alternating electric fields comprising exposing the cancer cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength, and exposing the cancer cell to an IGFR1 inhibitor, JNK inhibitor, RPS6 inhibitor or ERK inhibitor. Disclosed are methods of increasing treatment efficacy comprising applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor to the subject. Disclosed are methods of treating a subject having cancer comprising applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor to the subject. Disclosed are methods of reducing viability of cancer cells using an alternating electric field for a period of time, the alternating electric field having a frequency and field strength in combination with either an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor. Disclosed are methods of increasing apoptosis of a cancer cell comprising exposing the cancer cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength; and exposing the cancer cell to an IGFR1 inhibitor, JNK inhibitor, RPS6 inhibitor or ERK inhibitor.

Compositions and methods for increasing cancer cell sensitivity to alternating electric fields

Alternating electric fields (e.g., TTFields) may be induced in a target region in a subject's body by applying, during each of a plurality of first time intervals, a series of pulses of alternating current between electrode elements positioned on or in the subject's body. Immediately following each first interval of time, the electrode elements are allowed to cool. Although the pulses of alternating current within any given first time interval have amplitudes at a level that would cause overheating if the series of pulses was allowed to continue for one hour, each series of pulses does not, in fact, continue for one hour. To the contrary, each series of pulses is short enough to avoid overheating. Interleaving the cooling periods between the pulsing periods enables higher-current pulses to be used, and the use of those higher-current pulses can advantageously improve the efficacy of treatment.

Using interleaved cooling periods to increase the peak intensity of tumor treating fields

A reduction in viability of cancer cells (e.g., glioblastoma) and a reduction in tumor volume can be achieved by applying a 100-500 kHz (e.g., 200 kHz) alternating electric field to the cancer cells and inhibiting IL11 (interleukin-11) activity and optionally administering and anti-fibrotic agent. The inhibiting of IL11 activity may be accomplished, for example, by decreasing IL11 expression, inhibiting IL11 signaling, downregulating IL11, neutralizing IL11, blocking an IL11 receptor, administering an IL11 antagonist, administering an IL11 neutralizing antibody, or administering an IL11 receptor α (IL11Ra) neutralizing antibody.

Increasing cancer cells' sensitivity to tumor treating fields (TTFields) by inhibiting IL11 activity

Many drugs and other molecules cannot ordinarily traverse the blood brain barrier (BBB). However, when alternating electric fields at certain optimum frequencies (e.g., 100 kHz) are applied to the brain, the BBB becomes permeable to those molecules. When the alternating electric fields are discontinued, the BBB eventually recovers to its original impermeable state. Subsequently, re-application of alternating electric fields at the optimum frequencies will re-open the BBB. Ordinarily, many frequencies (e.g., 200 kHz) of alternating electric fields are either ineffective or less effective at inducing permeability than the optimum frequencies. But once the BBB has been opened by applying alternating electric fields at the optimum frequencies, alternating electric fields at non-optimum frequencies can maintain the permeability of a previously-opened BBB.

Using alternating electric fields to increase permeability of the blood brain barrier

Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.

Tumor treating fields (TTFields) can be delivered by implanting a plurality of sets of implantable electrode elements within a person's body. Temperature sensors positioned to measure the temperature at the electrode elements are also implanted, along with a circuit that collects temperature measurements from the temperature sensors. In some embodiments, an AC voltage generator configured to apply an AC voltage across the plurality of sets of electrode elements is also implanted within the person's body.

Delivering tumor treating fields (TTFields) using implantable transducer arrays

Disclosed are methods and compositions for preventing or disrupting mitosis of pluripotent stem cells, killing pluripotent stem cells, preventing or disrupting division of pluripotent stem cells, reducing the viability of pluripotent stem cells, slowing the progression or differentiation of pluripotent stem cells, and treating an ectopic pregnancy.

Compositions and methods of applying alternating electric fields to pluripotent stem cells

Disclosed are compositions for and methods of altering the electric impedance to an alternating electric field in a target site of a subject. Disclosed are compositions for methods of improving transport of a nanoparticle across a cell membrane of a cell.

Viral infections in a target region can be inhibited by imposing an alternating electric field in the target region for a duration of time. The alternating electric field has a frequency and a field strength such that when the alternating electric field is imposed in the target region for the duration of time, the alternating electric field inhibits infection of the cells in the target region by the virus. Optionally, the inhibition of viral infections using the alternating electric field approach can be combined with delivering an antiviral agent to the target region so that a therapeutically effective dose of the antiviral agent is present in the target region while the alternating electric fields are imposed.

Inhibiting viral infection using alternating electric fields

Autoinflammatory and mitochondrial disorders can be treated by positioning a plurality of electrodes in or on a subject's body, and applying an AC voltage between the plurality of electrodes so as to impose an alternating electric field through the tissue that is being affected by the autoinflammatory or mitochondrial disease. The frequency and field strength of the alternating electric field are selected such that the alternating electric field inhibits inflammation or mitochondrial disorders in the tissue.

Growing community of inventors

Kibbutz Gvat, Israel

Tali Voloshin-Sela