Tessa showcases preclinical promise of 'all-in-one' add-on to its cancer cell therapy, in march to the clinic
At Tessa Therapeutics, the big idea has been to adapt virus-specific T cells (VST) to target virally-associated tumors, and swarm cancer cells. Researchers believe these VSTs can be versatile, making superior CAR-Ts that can then be combined with an oncolytic virus and a checkpoint inhibition strategy. In its latest preclinical trial, the Singapore-based biotech has spotlighted one such “all-in-one” approach that they are now taking into the clinic.
The treatment, which is tailored for HER2-positive solid tumors, consists of two steps: First, investigators inject an oncolytic adenovirus into a tumor site, simultaneously killing tumor cells and secreting PD-L1 blocking antibodies and IL-12p70 cytokines. Then comes the CAR-T, which pillages the region systemically to clear out other cancer cells.
In head and neck squamous cell carcinoma xenograft models, Tessa reports, the combination improved survival to >100 days compared to approximately 25 days with either approach alone.
That’s significant as metastatic HER2-positive solid tumors remain incurable even with existing anti-HER2 targeted therapies, said Ivan Horak, Tessa’s president of R&D. He added:
What’s particularly encouraging from the preclinical study findings is that, it suggests the effectiveness of oncolytic adenovirus in mimicking the body’s anti-viral immune response to enhance the activity of T cells against HER2-positive cancer cells. The results support the scientific notion that locally-produced anti PDL1 antibody effectively protects T cells from the immunosuppressive tumor environment and activation cytokine IL-12p70 enhances tumor inflammation to improve T cells tumor penetration.
Baylor College of Medicine — Tessa’s collaborator for the preclinical study — will lead the Phase I, an IND for which will be submitted by the end of the year.
It will be a basket trial involving patients with different HER2-positive cancers, Horak said. According to a posting on clinicaltrials.gov, that spans bladder cancer, head and neck squamous cell carcinoma, cancer of the salivary gland, lung cancer, breast cancer, gastric cancer, esophageal cancer, colorectal cancer and pancreatic adenocarcinoma across 39 patients — though Tessa emphasizes that their plans could evolve as they prep the IND.