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WO-2026093944-A1 - MANUFACTURE OF CANCER CELLS IN A CLOSED AND STERILE SYSTEM

WO2026093944A1WO 2026093944 A1WO2026093944 A1WO 2026093944A1WO-2026093944-A1

Abstract

A method for generating modified cancer cells is provided. The method comprises obtaining a sample comprising unmodified cancer cells; separating unmodified cancer cells from other cell populations in the sample; and modifying the unmodified cancer cells in a cultivation chamber to produce modified cancer cells. The method is performed in a closed and sterile cell culture system. In typical aspects, the method is automated. A system for performing the method on a device and uses of the modified cancer cells are also provided.

Inventors

  • THOME KREUTZ, Fernando

Dates

Publication Date
20260507
Application Date
20251029
Priority Date
20241030

Claims (20)

  1. 1 . A method for generating modified cancer cells, comprising: obtaining a sample comprising unmodified cancer cells; separating the unmodified cancer cells from other cell populations in the sample; and modifying the unmodified cancer cells in a cultivation chamber to produce the modified cancer cells; wherein the method is performed in a closed and sterile cell culture system.
  2. 2. The method of claim 1 , wherein the modifying the unmodified cancer cells comprises adding an MHCII inducing agent to the unmodified cancer cells within the closed and sterile cell culture system.
  3. 3. The method of claim 2, wherein the MHCII inducing agent comprises a cytokine, an MHCII expression construct or an MHClI-expressing cell that will fuse with the cancer cells.
  4. 4. The method of claim 3, wherein the cytokine is selected from interferon-alpha (IFN-a), interferon-beta (IFN-|3), interferon-gamma (IFN-y), IL-4, IL-13, IL-23, tumor necrosis factor-alpha (TNF-a) or any combination thereof.
  5. 5. The method of claim 3 or 4, wherein the cytokine is IFN-y.
  6. 6. The method of any one of claims 1 to 5, further comprising incubating the modified cancer cells with a non-self antigen within the closed and sterile cell culture system.
  7. 7. The method of claim 6, wherein the non-self antigen is a non-human antigen.
  8. 8. The method of claim 6 or 7, wherein the non-self antigen is selected from thyroglobulin, 13-galactosidase, dextran, polylysine, tuberculin derived protein, ovalbumin (OVA), bovine serum albumin (BSA), sheep serum albumin, goat serum albumin, fish serum albumin, or keyhole limpet hemocyanin (KLH).
  9. 9. The method of claim 8, wherein the non-self is OVA.
  10. 10. The method of claim 8, wherein the non-self is KLH.
  11. 11 . The method of claim 8, wherein the non-self antigen is BSA.
  12. 12. The method of claim 6 or 7, wherein the non-self antigen is not BSA.
  13. 13. The method of claim 6 or 7, wherein the non-self antigen is selected from bovine, rabbit, murine, canine, or feline antigen.
  14. 14. The method of claim 6 or 7, wherein the non-self antigen is not a bovine antigen.
  15. 15. The method of any one of claims 1 to 14, wherein the unmodified cancer cells are derived from a solid tumor.
  16. 16. The method of claim 15, wherein the solid tumour is obtained from a subject during a biopsy procedure or during surgical removal of a tumour.
  17. 17. The method of claim 15 or 16, wherein the solid tumor is obtained from a patient with breast cancer, colorectal cancer, melanoma, ovarian cancer, pancreatic cancer, gastric cancer or prostate cancer.
  18. 18. The method of claim 15 or 16, wherein the solid tumour is obtained from a patient with prostate cancer.
  19. 19. The method any one of claims 15 to 18, wherein the solid tumour is fragmented, within the closed and sterile system, using enzymes to produce a sample of the unmodified cancer cells and other cell populations.
  20. 20. The method of any one of claims 1 to 19, wherein the separating is carried out using magnetized antibodies.

Description

MANUFACTURE OF CANCER CELLS IN A CLOSED AND STERILE SYSTEM Field The present disclosure relates to methods of generating modified cancer cells. In particular, the present disclosure relates to methods and systems for culturing and isolating modified cancer cells that can then be used for the treatment of patients with cancer. Background Major histocompatibility complex (MHC) is a cell surface molecule encoded by a large gene family in all vertebrates. The MHC gene family is divided into three classes: class I; class II; and class III. In U.S. Patent No. 9,320,785, cancer cells, while not typically known to express MHCII, were shown to be modified to present a non-self peptide in the context of MHCII to helper T cells and therefore effectively replace the function of APCs. The modified cancer cells are considered bifunctional, because they will also present a tumour-specific antigen in the context of MHCI to cytotoxic T cells. While these modified cancer cells where shown to be useful in autologous cancer cell vaccines, the methods of manufacturing modified cancer cells typically consists of using a large number of devices to perform small steps which can inevitably result in higher error rates and increased time requirements due to the need for manual interventions. A need exists for the development of a method and/or system for generating modified cancer cells that provides the public with a useful alternative. The background herein is included solely to explain the context of the disclosure. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge as of the priority date. Summary In an aspect, there is provided a method for generating modified cancer cells, comprising: obtaining a sample comprising unmodified cancer cells; separating the unmodified cancer cells from other cell populations in the sample; and modifying the unmodified cancer cells in a cultivation chamber to produce the modified cancer cells; wherein the method is performed in a closed and sterile cell culture system. In an aspect, the modifying the unmodified cancer cells comprises adding an MHCII inducing agent to the unmodified cancer cells within the closed and sterile cell culture system. In an aspect, the MHCII inducing agent comprises a cytokine, an MHCII expression construct or an MHCH-expressing cell that will fuse with the cancer cells. In an aspect, the cytokine is selected from interferon-alpha (IFN-a), interferon-beta (IFN- P), interferon-gamma (IFN-y), IL-4, IL-13, IL-23, tumor necrosis factor-alpha (TNF-a) or any combination thereof. In an aspect, the cytokine is IFN-y. In an aspect, the method further comprises incubating the modified cancer cells with a non-self antigen within the closed and sterile cell culture system. In an aspect, the non-self antigen is a non-human antigen. In an aspect, the non-self antigen is selected from thyroglobulin, 13-galactosidase, dextran, polylysine, tuberculin derived protein, ovalbumin (OVA), bovine serum albumin (BSA), sheep serum albumin, goat serum albumin, fish serum albumin, or keyhole limpet hemocyanin (KLH). In an aspect, the non-self is OVA. In an aspect, the non-self is KLH. In an aspect, the non-self antigen is BSA. In an aspect, the non-self antigen is not BSA. In aspect, the non-self antigen is selected from bovine, rabbit, murine, canine, or feline antigen. In an aspect, the non-self antigen is not a bovine antigen. In an aspect, the unmodified cancer cells are derived from a solid tumor. In an aspect, the solid tumour is obtained from a subject during a biopsy procedure or during surgical removal of a tumour. In an aspect, the solid tumor is obtained from a patient with breast cancer, colorectal cancer, melanoma, ovarian cancer, pancreatic cancer, gastric cancer or prostate cancer. In an aspect, the solid tumour is obtained from a patient with prostate cancer. In an aspect, the solid tumour is fragmented, within the closed and sterile system, using enzymes to produce a sample of the unmodified cancer cells and other cell populations. In an aspect, the separating is carried out using magnetized antibodies. In an aspect, the separating involves direct labeling of the unmodified cancer cells through positive selection thereof. In an aspect, the separating involves direct labeling of the other cell populations in the sample through positive selection thereof. In an aspect, the separating involves indirect labeling of the unmodified cancer cells through negative selection thereof. In an aspect, the other cell populations comprise lymphocytes and fibroblasts. In an aspect, the method further comprises transferring the unmodified cancer cells to the cultivation chamber within the closed and sterile system. In an aspect, the method further comprises expanding the unmodified cancer cells within the cultivation chamber within the closed and sterile system. In an aspect, the expanding occurs over a per