Novocure GmbH

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 a subject having a biopsy-only glioblastoma tumor 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 glioblastoma cells; administering a therapeutically effective amount of temozolomide (TMZ); and administering a therapeutically effective amount of a checkpoint inhibitor to the subject. Disclosed are methods of increasing survival of a subject having a biopsy-only glioblastoma tumor 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 glioblastoma cells; administering a therapeutically effective amount of temozolomide (TMZ); and administering a therapeutically effective amount of a checkpoint inhibitor to the subject.

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 a a Notch1 inhibitor or Hes5 inhibitor to the subject in need thereof. Disclosed are methods of preventing cancer recurrence in a subject having cancer comprising: applying an alternating electric field to a target site of the subject in need thereof; and administering a Notch1 inhibitor or Hes5 inhibitor to the subject in need thereof. Disclosed are methods of reducing cancer cell growth comprising: applying an alternating electric field to a population of cells comprising one or more cancer cells; and contacting a Notch1 inhibitor or Hes5 inhibitor to the population of cells. Disclosed are methods of sensitizing cancer cells to an alternating electric field comprising: applying an alternating electric field to a population of cells comprising one or more cancer cells; and contacting a Notch1 inhibitor or Hes5 inhibitor to the population of cells.

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 are methods of treating a subject in need thereof comprising applying an alternating electric field, at a frequency for a period of time, to a target site of the subject in need thereof; and administering a Trop-2 specific therapeutic to the subject in need thereof. The disclosed methods can also enhance the efficacy of a Trop-2 specific therapeutic, increase progression-free survival of a subject with cancer, decrease tumor growth and increase killing of cancer cells.

Disclosed are methods of increasing survival of 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 a checkpoint 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 a checkpoint inhibitor to the subject. In some aspects, the checkpoint inhibitor is Nivolumab, Pembrolizumab, or Atezolizumab. Also disclosed are methods of increasing survival of a subject having non-small cell lung 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 non-small cell lung cancer cells, and administering a therapeutically effective amount of a checkpoint inhibitor to the subject. Disclosed are methods of treating a subject having non-small cell lung 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 non-small cell lung cancer cells, and administering a therapeutically effective amount of a checkpoint inhibitor to the subject. In some aspects, the checkpoint inhibitor is ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), cemiplimab (trade name Libtayo), and dostarlimab (Jemperli), atezolizumab (Tecentriq), durvalumab (Imfinzi), or avelumab (Bavencio).

Disclosed are methods of treating a subject in need thereof comprising applying an alternating electric field, at a frequency for a period of time, to a target site of the subject in need thereof, and administering trastuzumab to the target site of the subject in need thereof. Disclosed are methods of increasing accumulation of trastuzumab at a target site of a subject in need thereof comprising applying an alternating electric field, at a frequency for a period of time, to the target site of the subject in need thereof; and administering trastuzumab to the target site of the subject in need thereof, wherein the accumulation of the trastuzumab increases at the target site compared to administering the trastuzumab at the target site without applying an alternating electric field. Disclosed are methods of inhibiting cancer cell proliferation or increasing apoptosis of cancer cells at a target site of a subject in need thereof comprising applying an alternating electric field, at a frequency for a period of time, to the target site of the subject in need thereof; and administering trastuzumab to the target site of the subject in need thereof, wherein cancer cell proliferation is inhibited or wherein apoptosis of cancer cells is increased.

Methods of treating cancer are provided. In some instances, the method comprises applying alternating electric fields to the abdomen of the subject at a frequency of 100 to 500 kHz, administering a checkpoint inhibitor to the subject, and administering systemic cancer therapy to the subject. In some instances, the cancer is pancreatic ductal adenocarcinoma.

Methods and kits treating a subject with a checkpoint inhibitor are provided by detecting expression levels of one or more biomarkers (e.g., cytokines and cytotoxic genes, immune cell functional regulators, naïve immune cell markers, regulatory T cell factors, and immune inhibitory receptors) in immune cells of a patient or subject with a condition (e.g., cancer) before and after exposure of tumor cells to alternating electric fields. Kits comprising nucleic acid probes for detecting the one or more biomarkers are also provided.