Medigene AG presented improved TCR-T cell functionality at a summit in Amsterdam from April 29 - May 1, 2024.

The presentation is available on Medigene’s website.

Overcoming the immunosuppressive solid tumor microenvironment (TME) stands as a major hurdle for durable TCR-T therapies in patients. The PD-1/PD-L1 axis blocks the activity of T cells in an environment with tumor cells that have PD-L1. The company's PD1-41BB CSP improves TCR-T cell functionality by replacing the inhibitory signaling domain of PD-1 with the activating signaling domain of 4-1BB, countering the tumor self-defense mechanism.

The data showed that TCR-T cells expressing the PD1-41BB CSP and three different 3S-TCRs that target the mKRAS G12V neoantigen have high specificity and sensitivity. Elevated interferon gamma secretion was observed only when TCR-T cells were stimulated with mKRAS G12V-positive tumor cells. No such secretion was observed when stimulated with any tumor or healthy cell expressing the naturally occurring wild-type KRAS protein.

The three S TCRs exhibited a remarkably high sensitivity to the mKRAS G12V neoantigen. They responded to activation even when there was a very low amount of mKRAS-G12V peptide. The combination of PD1-41BB and CSP significantly improved the function of TCR-T cells. The cells were able to continue killing cancer cells in 3D tumor spheroids, even after being exposed to the tumor multiple times. This highlights the strong anti-cancer effect of TCR-T cells.