On June 9, 2021 Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that compelling new pre-clinical data on its lead T cell receptor (TCR) candidate "TCR-4" targeting solid tumors combined with its PD1-41BB switch receptor to overcome the highly immunosuppressive solid tumor microenvironment (Press release, MediGene, JUN 9, 2021, https://www.pressetext.com/news/20210609044 [SID1234583776]). The data underpins Medigene’s decision to advance TCR-4 in PRAME-positive cancer.

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The presentations are being made as part of the TCR-based Therapies Summit, a Digital Event being held 8-10 June 2021. Both the presentation and the poster can be found on Medigene’s website: View Source

TCR-4 which specifically targets the PRAME cancer antigen in the context of HLA-A2 was combined with Medigene’s lead functional T cell enhancer, the PD1-41BB switch receptor, and evaluated pre-clinically against a set of key performance hurdles to determine safety and efficacy.

The safety of the TCR-T cells carrying both TCR-4 and PD1-41BB was demonstrated in vitro. There was no off-target toxicity: cells which did not express the target antigen PRAME, including a panel of normal healthy tissues (such as lung, bone, heart and kidney among others), were not killed. Furthermore, no toxicity was observed against HLA-A2 negative cells.

TCR-T cells carrying both TCR-4 and PD1-41BB demonstrated enhanced anti-cancer efficacy both in vitro and in vivo. In vitro, they were functionally more active against tumor cells expressing the PRAME target, producing increased levels of key cytokines (messenger molecules) and improving the sustainability of repeated killing activity. The improved performance was echoed in vivo. We had previously shown that TCR-T cells with TCR-4 alone were sufficient to eliminate PD-L1 negative melanoma tumors in vivo (AACR 2021). The new data come from a more challenging in vivo model of aggressively growing, PD-L1 positive melanoma and show that only TCR-T cells carrying the combination of both TCR-4 and PD1-41BB could eliminate tumors with these highly immunosuppressive characteristics.

Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "Tumors expressing PD-L1 are highly immunosuppressive making them the most challenging solid cancers in medicine. The results we have presented show the exquisite specificity and compelling functional potency of our enhanced TCR-T cells carrying the TCR-4 plus PD1-41BB combination against aggressively growing PRAME positive, PD-L1 positive solid tumor cells. This data gives Medigene the critical evidence it needs to select this impressive product candidate for further development towards clinical trials."