Medigene AG presents the company's proprietary T cell receptor (TCR) discovery process to obtain optimal Affinity 3S (sensitive, specific and safe) TCRs at the 21thAss Association for Cancer Immunotherapy (CIMT) Annual Meeting in Mainz from May 15 - 17, 2024. Data presented also shows the clear benefit of adding the PD1-41BB costimulatory switch protein (CSP) to further armor and enhance these 3S TCR-T cells, which enables them to overcome the immunosuppressive tumor microenvironment. The poster with the title "Selection of superior KRAS G12V mutation-specific T cell receptors with unique characteristics for 3rd generation armored and enhanced T cell therapy" will be available on May 15, 2024, following the presentation on Medigene's website: The presented data highlighted the specificity and sensitivity of TCR-T cells co-expressing the PD1-41BB CSP alongside one of three distinct 3S TCRs targeting the mKRAS G12V neoantigen.

These TCR-T cells displayed markedly increased secretion of interferon gamma (IFNg) observed upon TCR-T cell stimulation with mKRAS G12V-positive tumor cells, contrasting with the absence of IFN g secretion upon stimulation with any tumor or healthy cell expressing naturally occurring wild-type KRAS protein. All three 3S TCRs also demonstrated high sensitivity to the mKRAS G 12V neoantigen, as demonstrated by their activation in response to extremely low levels of mKRAS-G12V peptide. Conc Concurrent expression of the PD1-41 BB CSP significantly augmented TCR-T cell functionality, enabling sustained cytotoxicity targeting 3D tumor spheroids across multiple rounds of tumor exposure.

This underscores the potent anti-cancer efficacy of the TCR-T cells. From a safety perspective, all three 3S TCRs combined with the PD1-41BBCSP demonstrated favorable safety profiles, with no IFNg secretion or cytotoxicity when exposed to healthy cells from major tissues or organs, confirming their selective cytotoxicity towards cancer cells while sparing healthy tissue from toxicity.