Planegg/Martinsried (pta038/30.03.2021/22:30) - 30 March 2021. Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, announces 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. 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: https://jitc.bmj.com/content/9/3/e002035
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."
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.
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Medigene AG (FSE: MDG1, Prime Standard, ISIN DE000A1X3W00) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.
For more information, please visit www.medigene.com
About Medigene's TCR-Ts
TCR-T technology arms a patient's own T cells with tumor-specific T cell receptors. The T cell receptor-modified T cells (TCR-T cells) are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient's tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient's T cells outside the body (ex vivo).
Medigene is conducting a Phase I/II clinical trial of its TCR-T candidate MDG1011 in the blood cancer indications AML and MDS. In addition, Medigene is establishing a pipeline of TCRs and has collaborations with bluebird bio, Inc. and Cytovant Sciences HK Ltd. addressing solid tumor indications.
This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.
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