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EP-4740209-A1 - ELECTRIC FIELD THERAPY

EP4740209A1EP 4740209 A1EP4740209 A1EP 4740209A1EP-4740209-A1

Abstract

A method for improving electric field therapy for delivering to a patient with a tumor, wherein the regimen parameters are selected for the profile of the tumour. Also described are methods of electric field therapy, methods for treating tumours employing electric field therapy, and devices programmed to deliver electric field therapy regimens.

Inventors

  • BULLOCK, CHRISTOPHER
  • NARAYANAN, ASHWIN
  • ZHAO, Jinwei
  • OLUKOGA, Oluwatomisin

Assignees

  • QV BIOELECTRONICS LTD

Dates

Publication Date
20260513
Application Date
20240704

Claims (20)

  1. 1. A method for improving electric field therapy for delivering to a patient with a tumor which comprises: (i) receiving, by a processor of a computer system, a genetic and/or epigenetic and/or molecular and/or transcriptomic profile of the tumour; (ii) generating an analysis of the tumour from the received data; (iii) determining electric field therapy regimen parameters selected for the analysis of the tumour; and (iv) configuring an electric field therapy device to deliver electric field therapy employing those parameters.
  2. 2. A method as claimed in claim 1 wherein the profile of the tumour comprises the profile of the whole tumour.
  3. 3. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the profile of one or more regions of the tumour.
  4. 4. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the profile of one or more cell populations within the tumour.
  5. 5. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the genetic profile of the tumour.
  6. 6. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the epigenetic profile of the tumour.
  7. 7. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the molecular profile of the tumour.
  8. 8. A method as claimed in any one of the preceding claims wherein the profile of the tumour comprises the transcriptomic profile of the tumour. P-000050-WO-PCT-QVB
  9. 9. A method as claimed in any one of the preceding claims wherein the profile of the tumour is obtained by RNA sequencing.
  10. 10. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the frequency of the electric field therapy regimen.
  11. 11. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the amplitude of the current of the electric field therapy regimen.
  12. 12. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the amplitude of the voltage of the electric field therapy regimen.
  13. 13. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the electric field strength of the electric field therapy regimen.
  14. 14. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the direction of the current of the electric field therapy regimen.
  15. 15. A method as claimed in any one of the preceding claims wherein the regimen parameters comprise the duration of treatment of the electric field therapy regimen.
  16. 16. A method as claimed in any one of the preceding claims wherein the tumour is glioblastoma.
  17. 17. A method as claimed in claim 16 wherein the profile comprises the proneural, classical, and/or mesenchymal subtype profile.
  18. 18. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises multiple electrodes.
  19. 19. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises multiple electrodes implanted into the tumour or, following surgical resection, the tumour resection margin. P-000050-WO-PCT-QVB
  20. 20. A method as claimed in any one of the preceding claims wherein the electric field therapy comprises a biphasic injectable electrode which comprises a plurality of solid particles and a transporter phase, wherein both the solid particles and the transporter phase comprise poly(3,4- ethylenedioxythiophene)polystyrene sulfonate, injected into a tumour cavity following surgical resection.

Description

ELECTRIC FIELD THERAPY FIELD The present specification relates to electric field therapy. More specifically the present specification relates to a method of improving electric field therapy for administering to a patient with a tumour employing regimen parameters selected for the profile of the tumour. BACKGROUND Electric field therapy (EFT), sometimes referred to as electrotherapy, involves the use of electrical energy in medical treatment and can apply to a variety of treatments, including the use of electrical devices such as deep brain stimulators (DBS) for neurological disease such as Parkinson's disease. Electric field therapy can also be used as a physical therapy for muscle stimulation, pain management and wound healing for example, and may be used for the treatment of psychological symptoms for example anxiety, insomnia, depression, hypervigilance, and obsessive compulsive disease. Electric field therapy, typically involving the use of an electrical waveform in order to generate low-intensity electric fields alternating at an intermediate frequency (generally 10 to 600 kHz) using electric field of strength (E) ~ 1-5 Vcm-1, is currently being investigated as a treatment modality for several types of solid malignant tumours including lung cancer, liver cancer, gastric cancer, pancreatic cancer, malignant pleural mesothelioma and ovarian cancer. Electric fields are believed to interfere with mitosis, where dipole molecules like tubulin dimers of microtubules align with the applied field leading to improper polymerization and early metaphase exit. Furthermore, cells in the final stage of mitosis (telophase) are subject to non-uniform E that create dielectrophoretic (DEP) forces moving particles toward the furrow, prompting DNA damage and cellular suicide. (Jenkins et al.; Adv. Sci.2021,8, 2100978; https://doi.org/10.1002/advs.202100978). Electric field therapy has also been employed in combination with chemotherapy. Electric field therapy has been demonstrated clinically to be an effective treatment for glioblastoma (GBM) (previously glioblastoma multiforme), the most common type of primary brain tumours in adults. In phase III multi-centre clinical trials, electric field therapy has been shown to increase patient overall survival to 21 months when used as an addition to surgery (for example surgical resection), chemotherapy and radiotherapy (Stupp et al.; JAMA; 2017; 318(23):2306-16; doi: 10.1001/jama.2017.18718.). The electric field therapy delivers alternating sinusoidal electrical fields at specific frequencies (50 - 300 kHz) to the head slowing the growth of recurrent tumours and extending patient survival (Kirson et al.; PNAS; 2007; 104(24):10152-7; doi:10.1073/pnas.0702916104). Malignant tumours have highly diverse profiles both at the inter-tumour level (between different tumours) and intra-tumour level (within the same tumour) including within the tumour microenvironment itself. Regional differences within the tumour impose different selective pressures on tumour cells, leading to a wider spectrum of dominant subclones in different spatial regions of the tumour. Tumours may exhibit a combination of genetic, epigenetic, molecular and/or transcriptomic variabilities: genetic variability is either the presence of, or the generation of, genetic differences; epigenetic variation refers to modifications to DNA that do not alter the underlying nucleotide sequence, but can influence behaviour, morphology, and physiological phenotypes by affecting gene expression and protein synthesis; molecular variability is the changes in the nucleic acids (DNA/RNA) and/or proteins as well as in their interactions, which can affect the biological activity within a cell and/or tissue; and transcriptomic variability refers to the to changes in gene expression dues to changes in the RNA molecules which includes protein coding (mRNA) as well as non-coding RNAs produced in a particular cell or tissue. Tumour variability introduces significant challenges for effective drug treatment strategies. Traditionally, glioblastoma has been categorised according to three molecular subtypes; proneural, classical, and mesenchymal with many patients exhibiting multiple subtypes within the same tumour. Variability increases with time, and not only can more than one subtype be found within the same tumour at the same time, but they may also occupy spatially distinct regions. In multiple biopsies taken from the same tumour, the proneural subtype was predominantly found at the leading edge and in regions of invasion, whilst the mesenchymal subtype was mostly found in more hypoxic regions such as pseudopalisades or the necrotic core (Heiland et al, Mol. Cancer Res. 2018, 16, 655). This heterogeneity of glioblastoma adds to the complexity of treatment and poor overall survival times. The present inventors have found that different tumour profiles react differently to different electric field therapy regimens, where the regimen involves f