VST – Combinations

Virus-Specific T Cells & Chimeric Antigen Receptors

Engineering Tessa’s Virus-Specific T Cells (VSTs) with a Chimeric Antigen Receptor (CAR) allows us to target our treatments towards multiple solid tumors. This combined platform utilizes the strong qualities of persistence, durability and tumor penetration of a VST, while maintaining the antigen specificity and cytotoxicity of a CAR.

Glypican-3 (GPC3) CAR VSTs

GPC3 is a protein that is significantly expressed on major cancers. It is expressed on the surface of approximately 80% of hepatocellular carcinoma tumors (HCC, the most common form of liver cancer) and approximately 25% of lung cancers, making it a good target for cancer immunotherapy treatments. Tessa has developed a proprietary GPC3-Chimeric Antigen Receptor (CAR) construct which enables the targeting of these GPC3-positive tumors.

Other Advanced CAR Targets

Tessa has a range of other CAR targets in various stages of pre-clinical development. These CAR constructs will be explored in various combinatorial strategies involving VSTs as well as oncolytic viruses.

VSTs & Antibodies

Antibody biologics are highly complementary to Tessa Therapeutics’s core VST platform. Tessa’s advanced humanized monoclonal antibody discovery and engineering capabilities allow us to develop next generation antibodies as well as novel targets for CAR target discovery and development.

Checkpoint Inhibitors

Checkpoint inhibitors are a class of antibodies that help unleash the killing power of T cells by “releasing the brakes” on the immune system, leading to stronger cancer-killing responses. Checkpoint inhibitors may be utilized as stand-alone treatments, or in synergistic combination with other cancer immunotherapy strategies.

Expanding on the current HPVST Phase I clinical trial, which has shown early clinical significance in the treatment of HPV-associated cervical and oropharyngeal carcinoma, a sub-cohort of patients is to be treated using a combination of Tessa’s HPVSTs and checkpoint inhibitors.

This synergistic combination holds the promise of better patient survival outcomes.

Next Generation VST Strategies

Tessa is currently developing next generation VST strategies that may potentially overcome the immunosuppressive environment present in solid tumors. One of these strategies involves the development of bispecific engager systems. Upon recognition of a tumor antigen by the single chain variable fragment (ScFV) on a CAR, engager molecules are released, which then recruit additional T cells/ NK cells to attack these cancer cells in a secondary immune response.

Tessa aims to utilize a multi-pronged treatment approach to potentially overcome the immunosuppressive solid tumor environment. This holds the promise of providing patients with effective immunotherapy solutions for some of these “difficult to treat” solid tumor indications.

VSTs & Oncolytic Viruses

Oncolytic viruses offer the potential to enhance Tessa Therapeutics’ core VST platform, and extend our platform to treat a range of major solid tumors. By infecting and destroying these cancer cells, oncolytic viruses, in combination with VSTs, are able to redirect a potent anti-viral and sustained immune response against the tumor.

In addition, Tessa’s proprietary oncolytic virus has been genetically modified to produce select antibodies and immunomodulatory cytokines which further enhance T Cell activation and tumor killing. We are now preparing for a Phase I clinical trial which combines oncolytic viruses and VSTs to treat squamous cell head and neck cancers.

Lytic Viral Infection

Cancer cells often downregulate their expression of cancer-associated antigens in order to evade the immune system. Oncolytic viruses preferentially and progressively infect and destroy cancer cells in the solid tumor. Dying tumor cells then release tumor-specific and viral antigens which further stimulate and complement our VSTs target recognition and killing ability.

This way, we create continuous cycles of cancer cell destruction that recapitulates a natural, lytic viral infection clearance by our immune cells.

Engaging the Innate and Adaptive Immunity

VSTs are our potent killer cells. However, innate immune cells such as NK cells also show tumor killing ability. By mimicking the lytic viral infection, the use of oncolytic viruses will help to activate the innate immune response, including NK cells and antigen presenting cells.

This way, we engage both arms of immune system, innate and adaptive, to create a shift in the tumor microenvironment from immune-suppressive to tumor-suppressive. Our understanding of the body’s anti-viral immune response allows us to design next generation cancer treatments that redirects the body’s own anti-viral immunity to attack and destroy cancer.