On September 16, 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 the cellular functionality of its lead T cell receptor-modified T cell therapy (TCR-T) candidate containing the PRAME-specific T cell receptor (TCR) "TCR-4" combined with Medigene’s PD1-41BB switch receptor (Press release, MediGene, SEP 16, 2021, https://www.pressetext.com/news/20210916008 [SID1234587829]).

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In vitro and in vivo, the co-expression of the PD1-41BB switch receptor and TCR-4 on TCR-T cells led to an enhanced response to antigen. In vitro, co-expression enhanced TCR-T proliferation as well as tumor cell killing and increased the release of cytokine messengers, particularly of effector, stimulatory and chemo-attractive cytokines. In an in vivo model, expression of PD1-41BB together with TCR-4 showed the same effects as during the in vitro experiments and promoted tumor clearance substantially. Importantly, co-expression of TCR-4 and the PD1-41BB switch receptor did not impede the favorable preclinical safety profile.

The ePoster 1007P is entitled "T cells transgenic for a highly potent PRAME-specific TCR and a chimeric PD1-41BB co-stimulatory receptor represent a promising approach for the treatment of solid tumors." It will be presented as part of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress being held virtually on 16-21 September 2021. The poster can be found on Medigene’s website: View Source

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "The PD1-41BB switch receptor clearly improves TCR-T performance. With PD1-41BB, TCR-4 T cells showed a higher percentage of poly-functional T cells than without. With the PD1-41BB switch receptor co-expressed, a higher proportion of single cells secreted 4-10 cytokines simultaneously. Furthermore, with PD1-41BB co-expression we saw a high number of effector and stimulatory cytokines, and raised levels of chemo-attractive cytokines, which help T cells to migrate towards their target tissue in the body. These data underline our decision to advance the development of the PD1-41BB switch receptor in tandem with TCR-4 in PRAME-positive solid tumors."