On April 25, 2022 Medigene AG ( View Source) (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology company focusing on the development of T-cell-based cancer therapies, reported the publication of a new peer-reviewed publication in the journal Cancers showing that the chimeric PD1-41BB receptor augments antigen-specific activity of T cell receptor-modified T cells (TCR-T cells) while retaining a favorable safety profile (Press release, MediGene, APR 25, 2022, View Source [SID1234612914]). The data suggests that the PD1-41BB switch receptor is a promising tool to overcome PD-1/PD-L1 inhibition in the tumor microenvironment of solid cancer without the negative side-effects associated with the use of systemic PD-1/PD-L1 checkpoint inhibitor antibodies.
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The inhibitory PD-1/PD-L1 checkpoint axis is a negative influence on T cell efficacy, fitness and persistence. Systemic use of anti-checkpoint antibodies benefits clinical outcomes in some patients but is often associated with drug-related immunotoxicities. Medigene developed the PD1-41BB chimeric receptor, which is exclusively expressed in the therapeutically active TCR-T cells to switch inhibitory PD-1/PD-L1 interactions into positive signals that enhance antigen-specific TCR-T cell function.
The publication describes how Medigene isolated the HLA-A2-restricted, PRAME-specific T cell receptor (TCR) "TCR-4" from blood from healthy donors (tapping a non-tolerized T cell repertoire) and how TCR-T cells expressing TCR-4 and the PD1-41BB switch receptor show improved effector functions, a favorable safety profile in vitro, reject tumors in vivo and have a poly-cytokine profile upon antigen-specific activation.
Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: "We are proud of the high quality of this TCR that we identified and subsequently characterized using our proprietary high-throughput TCR screening technology. Also, after more than 40 years in T cell research, I am deeply impressed by how much our PD1-41BB switch receptor enhances the functional properties of TCR-T cells. BioNTech has also recognized the potential in our technologies and purchased the "TCR-4" program as well as received licenses to the PD1-41BB switch receptor. We believe that these and other approaches which we are developing will be the key to obtaining greater efficacy in TCR-T immunotherapies against solid cancers."
The Cancers publication is titled "T-Cells Expressing a Highly Potent PRAME-Specific T-Cell Receptor in Combination with a Chimeric PD1-41BB Co-Stimulatory Receptor Show a Favorable Preclinical Safety Profile and Strong Anti-Tumor Reactivity" and has recently been published online: View Source