THE TVAX® PLATFORM
TVAX Biomedical is developing an exciting innovative approach to cancer treatment (TVAX Immunotherapy®) that offers the promise of improved clinical outcomes for patients with any type of cancer, low toxicity and the potential for fundamentally changing the way cancer is treated.
TVAX Immunotherapy is a unique personalized combination of cancer cell vaccination and activated “killer” T cell treatment. TVAX Immunotherapy is built upon more than 50 years of intensive scientific and medical research into the interactions between cancer and the immune system. This novel, proprietary immunotherapy platform potentially provides a paradigm shift in the systemic treatment of cancer.
The key distinction between TVAX Biomedical and other cancer immunotherapy companies is that TVAX Immunotherapy uses BOTH cancer vaccine pretreatment to generate cancer neoantigen-specific T cells AND activated “killer” T cells to safely and effectively treat cancer.
How It Works
Surgery : Surgical removal of the patient’s cancer tissue is required to generate a personalized vaccine. TVAX converts cancer tissue into a large number of individual cancer cells in its cGMP manufacturing facility. The cancer cells are inactivated so that they can’t produce a new cancer, are combined with a potentiating agent and are used to vaccinate the patient.
Vaccination : Cancers accumulate large numbers of genetic changes, a portion of which are translated into proteins that are recognized by the patient’s immune system (neoantigens). Vaccinating a patient with their own cancer cells generates potent neoantigen-specific immune responses that produce large numbers of partially activated neoantigen-specific T cells. By itself, vaccination has little effect on the patient’s cancer because the partially activated neoantigen-specific T cells cannot kill cancer cells. TVAX Immunotherapy solves this problem by converting the partially activated T cells into fully activated “killer” T cells.
T Cell Activation : The TVAX solution is to collect the partially activated killer T cell precursors generated by vaccination from the patient’s blood. These killer T cell precursors are converted into activated neoantigen-specific killer T cells in the TVAX manufacturing facility using our proprietary methods.
T Cell Delivery : When those activated and expanded neoantigen-specific killer T cells are returned to the patient’s body, they target sites of inflammation and disease, including cancer. These killer T cells enter cancer tissue and destroy cancer cells. The treatment process has low toxicity because neoantigen-specific killer T cells kill cancer cells but not normal cells.
Advantages of neoantigen-specific cellular immunotherapy based on the science:
- Can be used to treat any cancer
- Would be expected to be effective against any type of cancer because cancer types are similarly immunogenic
- High safety profile : Minimal toxicity because neoantigen-specific effector/killer T cells only kill cancer cells, not normal cells
Lead Product Candidate
The company’s lead product candidate TVI-Brain-1 is focused on treating brain cancer and is support by positive Phase 2 clinical data, as well as extensive preclinical and Phase 1 safety studies. Based on these supportive data, the US Food and Drug Administration (FDA) has authorized Fast Track Designation for TVAX Biomedical to perform a Phase 2b clinical trial to test TVI-Brain-1 as a treatment for glioblastoma.
In addition, extensive proof-of-concept and safety data have been generated to support the use of TVAX Immunotherapy in several other cancer indications.
Manufacturing Overview of TVAX® Immunotherapy
cGMP manufacturing facility.
Manufacture of the attenuated autologous cancer cell vaccine
Cancer tissue that is obtained from surgery and shipped to the TVAX manufacturing facility is converted into a sterile vaccine. The vaccine is stored frozen and shipped to the treatment site where they are combined with an immunologic adjuvant.
Manufacture of activated effector (killer) T cells
White blood cells are obtained from vaccinated patients using leukapheresis. The leukapheresis product is shipped to the TVAX manufacturing facility where the mononuclear white blood cells are converted into effector/killer T cells. The activated T cell product is then shipped to the clinical site where the cells are returned to the patient.
Support References
References supporting safety and efficacy of cancer neoantigen-specific effector/killer T cells
Preclinical rodent (from more than 100)
Holladay FP, Heitz T, Chen Y-L, Wood, GW. (1992) Successful treatment of a malignant rat glioma with cytotoxic T-cells. Neurosurgery. 31:528-33. PMID:1407433
Geiger JD, Wagner PD, Shu S, Chang AE. (1992) A novel role for autologous tumour cell vaccination in the immunotherapy of the poorly immunogenic B16-BL6 melanoma. Surg Oncol. 1:199-208. PMID:1341252
Parviz M, Chin CS, Graham LJ, Miller C, Lee C, George K, Bear HD. (2003) Successful adoptive immunotherapy with vaccine-sensitized T cells, despite no effect with vaccination alone in a weakly immunogenic tumor model. Cancer Immunol Immunother. 52:739-50. PMID: 12827306
Preclinical canine
Flesner BK, Wood GW, Gayheart-Walsten P, Sonderegger FL, Henry CJ, Tate DJ, Bechtel SM, Donnelly LL, Johnson GC, Kim DY, Wahaus TA, Bryan JN, Reyes N. (2020) Autologous Cancer Cell Vaccination, Adoptive T Cell Transfer, and Interleukin-2 Administration Results in Long-Term Survival for Companion Dogs with Osteosarcoma. J Vet Intern Med. 34:2056-67. PMID: 32649801
Human
Wood GW, Holladay FP, Turner T, et al. (2000) A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma. J Neurooncol. 48:113-20. PMID:11083074
Chang AE, Aruga A, Cameron MJ, et al. (1997) Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2. J Clin Oncol. 15:796-807. PMID:9053507
Sloan AE, Dansey R, Zamorano L, et al. (2000) Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 9:e9, 2000. PMID:16817692
Chang AE, Li Q, Jiang G, et al. (2003) Phase II trial of autologous tumor vaccination, anti-CD3-activated vaccine-primed lymphocytes, and interleukin-2 in stage IV renal cell cancer. J Clin Oncol. 21:84-90. PMID:12610189
Dudley ME, Wunderlich JR, Yang JC, et al. (2005) Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 23:2346-57. PMID:15800326
Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, Levy D, Kubi A, Hovav E, Chermoshniuk N, Shalmon B, Hardan I, Catane R, Markel G, Apter S, Ben-Nun A, Kuchuk I, Shimoni A, Nagler A, Schachter J. (2010) Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 16:2646-55. PMID:20406835
Pilon-Thomas S, Kuhn L, Ellwanger S, Janssen W, Royster E, Marzban S, Kudchadkar R, Zager J, Gibney G, Sondak VK, Weber J, Mulé JJ, Sarnaik AA. (2012) Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma. J Immunother. 35:615-20. PMID:22996367
Shimizu K, Kotera Y, Aruga A, et al. (2012) Clinical utilization of postoperative dendritic cell vaccine plus activated T-cell transfer in patients with intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 19:171–8. PMID:21874278
Shimizu K, Kotera Y, Aruga A, et al. (2014) Postoperative dendritic cell vaccine plus activated T-cell transfer improves the survival of patients with invasive hepatocellular carcinoma. Hum Vaccin Immunother. 10:970-6. PMID:24419174