On March 30, 2021 Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported the publication of a peer-reviewed paper entitled, "Development of a CD8 co-receptor independent T cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy" covering preclinical research on a T cell receptor (TCR) specific for a peptide derived from the MAGE-A4 protein in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, MediGene, MAR 30, 2021, View Source [SID1234577444]). The research was conducted by Medigene’s scientists in collaboration with scientists from bluebird bio, Inc. (bluebird bio, NASDAQ: BLUE). The paper was published online: View Source

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The paper describes the discovery and characterization of a MAGE-A4-specific TCR and provides detailed scientific information highlighting the robust potency and exquisite specificity of this TCR against a MAGE-A4-derived peptide.

This MAGE-A4-specific TCR is the most advanced program in Medigene’s collaboration with bluebird bio. This TCR differs from other MAGE-A4 TCRs currently in development elsewhere as it works independently of the T cell co-receptor CD8, which is found on killer T cells. As shown in the paper, this enables T cells equipped with this MAGE-A4 TCR to detect and kill tumor cells expressing MAGE-A4 in a preclinical setting, including helper T cells which express CD4 and not CD8.

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: "We are delighted to see the high quality of our collaborative research with bluebird bio recognized by this scientific publication. This MAGE-A4-specific TCR, being CD8 co-receptor independent, can activate MAGE-A4-specific responses in either CD4 helper or CD8 killer T cells. In this way, the TCR enables the broadest functional T cell response against MAGE-A4-positive tumor cells and, as demonstrated in preclinical in vivo models, strong control of tumor growth.
Our allogeneic T cell priming, and selection technology was used very successfully to isolate this TCR. This technology is well suited to finding such non-mutated, high avidity TCRs specific for different antigens which we believe will be key to developing next generation TCR-T cells for solid cancer."

Scientific Information
The MAGE-A4-specific HLA-A2-restricted TCR was isolated using Medigene’s allogeneic priming technology to stimulate and screen T cells from an HLA-A2-negative donor for cells with the desired specificity. In preclinical research, the TCR has a favorable activity profile and superior in vivo potency compared to other specific MAGE-A4 TCRs tested (including those isolated from HLA-A2-positive donors who have tolerized T cell repertoires to self-antigens presented by HLA-A2). This non-mutated, high avidity MAGE-A4-specific TCR is CD8 co-receptor-independent, allowing effector functions to be elicited in CD4 helper T cells transduced to express the TCR. These CD4 TCR-T cells not only supported an anti-tumor response by direct killing of MAGE-A4-positive tumor cells, but also upregulated certain properties associated with helper function, such as surface marker expression and release of key cytokines.