Tumor Infiltrating Lymphocyte (TIL) Therapies

TILs are part of the body’s natural response to cancer:

  • The cells of the immune system perform immunosurveillance while circulating throughout the body
  • As part of the normal immune response, TIL migrate to the tumor site through recognition of chemokines produced by the tumor. TIL recognize tumors through tumor-specific antigens (TSAs) and can cause lysis to tumor ce
  • Solid tumors are extremely heterogeneous. Studies suggest that TIL from each individual are unique and polyclonal, which means that TIL may be able to recognize an array of known tumor antigens and unique patient-specific antigens TILs are Important for helping to eradicate tumor cells.

They recognize and eradicate tumor cells in three steps

  • TILs recognize the TSAs on the surface of tumor cells
  • TILs can become activated and release perforin, a pore-forming protein
  • The newly formed pores allow for the delivery of granzymes, which causes lysis of target cancer cells.

Given the frequently reported inadequacies of conventional cancer therapies and the growing need for personalized medicines, there is a surge in demand for TIL-based therapies. Considering the encouraging clinical trial data and the rising need for safe and efficacious therapies, TIL-based therapies have generated significant enthusiasm among medical R&D professionals in cancer centers around the world. Based on multiple clinical and preclinical stage success stories, TIL-based therapies are anticipated to carve out a significant share of the multi-billion-dollar cance immunotherapy market.

Why is TZ 102 so important to T-cell (TIL) Therapies:

Currently, approximately three-to-five percent (3-5%) of the T-cells Infused into a patient enter the Tumor Micro-Environment from the blood vasculature. This means 95% of the cells generated are wasted or, worse, rampage through the body causing side effects.

TZ 102 Enables Tumor Infiltrating Lymphocytes (TILs) to ‘home’, that is, to be directed to the tumor micro-environment more effectively from the blood vasculature by improving Tumor Infiltrating Lymphocyte cell rolling, tethering on the endothelial cells of the blood vessels and promoting their extravasation through the blood-vessel walls, enabling their transmigration into the tumor micro-environment. This resulted in 300-500% more T-cells reaching the tumor-micro-environment from the blood vasculature.

In addition to enabling 300-500% more T-cells to enter the tumor-micro-environment from the blood stream, TZ 102 increases T-cell binding to tumors i.e. increases T-cell synapse formation with the tumors and increases T-Cell intra-tumor penetration. TZ 102 also increases the number of T-cells expressing FASL and intracellular Granzyme B and Perforin, all consistent with enhanced T-cell cytoxicity for increased tumor killing.

TZ102 TIL Therapy Advantages:

  • Potential to further improve overall response rate and overall survival for cancer patients with solid tumors undergoing personalized Tumor Infiltrating Lymphocyte (TIL) therapy. Preclinical, technical-proof-of-concept data generated at MD Anderson Cancer Center, Harvard Medical Center, and the University of Pennsylvania point to the potential of TZ102 to increase the objective response rate of TIL therapies, currently in the 35-50% range, for treatment of solid tumors such as melanoma, pancreatic cancer, head-and-neck cancer, breast cancer, and prostate cancer. Preclinical data also points to a potential improvement in the complete response rate and overall survival.

  • Potential for improved safetycompared to genetically engineered T-cell therapies. Unlike genetically modified T-cell therapy, TZ 102 TIL Therapy is innate to the individual patient, translating to greater patient safety.

  • Potential to Further accelerate speed of patient treatmentBy enabling T cells to reach tumors more efficiently, utilizing TZ 102, in combination with TIL cells, could potentially result in lower required TIL cell count for patients, resulting in fewer weeks required to manufacture TIL therapies and faster treatment. This is especially important for patients with stage four (4) cancers. The current TIL standard-of-care requires each patient to receive as many as 100 billion TIL cells. This cell-expansion process takes several weeks. Based on preclinical data, there is a potential with TZ 102 to enable a significantly smaller number of TILs for improved efficacy outcomes for patients. Fewer therapeutic cells required translate to less time spent at the expansion step.

  • Potential to Further Lower Cost of Patient CareIn substantially reducing the required cell dose, TZ 102 has the potential to lower manufacturing cost of Tumor Infiltrating Lymphocyte therapies because less time and fewer cells would be required for the same therapeutic effect. This could mean that TZ 102 can potentially enable such T-cell therapy (TILs) to become affordable for the more than one hundred million cancer patients worldwide.