Novocure GmbH

Viability of cancer cells (e.g., glioblastoma cells) can be reduced by applying an alternating electric field with a frequency between 100 and 500 kHz to the cancer cells for about 3-10 days and administering a checkpoint inhibitor to the cancer cells.

Disclosed are methods of treating a subject in need thereof comprising applying an alternating electric field to a target site of the subject in need thereof; and administering one or more CD 137 agonists to the subject in need thereof. Disclosed are methods of promoting an effector T (Teff) cell immune response, decreasing immune suppression, decreasing mitochondrial respiration of regulatory T (Treg) cells, and reducing expansion of Treg cells in a subject in need thereof comprising applying an alternating electric field to a target site of the subject in need thereof; and administering one or more CD 137 agonists to the subject in need thereof.

Disclosed are methods of treating of a subject having cancer comprising applying an alternating electric field to a target site of the subject for a period of time, wherein the target site comprises one or more cancer cells, wherein the subject has an isocitrate dehydrogenase mutation (IDHmut). Disclosed are methods of treating a subject comprising identifying a subject with an IDHmut; and applying an alternating electric field to a target site of the subject for a period of time, wherein the target site comprises one or more cancer cells.

Certain substances (e.g., large molecules) that ordinarily cannot traverse the cell membrane of cells can be introduced into cells by applying an alternating electric field to the cell 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 cell membrane. Once the permeability of the cell membrane has been increased, the substance is able to cross the cell membrane. This approach is particularly useful in the context of cancer cells (e.g., glioblastoma).

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.

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.

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.

Compositions, systems, and advanced methods for reducing viability of cancer cells and treating cancer, as well as preventing an increase of volume of a tumor present in a body of a living subject, are disclosed. The systems and methods involve application of an alternating field concurrently with administration of at least one composition that inhibits at least one of immunomodulatory cytokine such as (but not limited to) macrophage migration inhibitory factor (MIF), MHC class I chain-related polypeptide A (MICA), and/or MHC class I chain-related polypeptide B (MICB).

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, kits, systems, and methods for reducing viability of cancer cells and treating cancer, as well as reducing a volume of a tumor and/or preventing an increase in volume of a tumor present in a body of a living subject, are disclosed. Also disclosed are methods of increasing reactive oxygen species (ROS) in cancer cells, along with methods of enhancing cytotoxicity of at least one thioredoxin reductase inhibitor and/or at least one glutathione inhibitor against cancer cells. The systems and methods involve application of an alternating field in combination with administration of at least one composition comprising at least one thioredoxin reductase inhibitor and/or at least one glutathione inhibitor.