Medigene's MAGE-A4-specific TCR-Ts detect and fight cancer cells independent of CD8 co-receptor
- Category: DNA RNA and Cells
- Published on Tuesday, 10 November 2020 14:33
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PLANEGG/MARTINSRIED, Germany I November 9, 2020 I Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, is pleased to present a poster detailing pre-clinical research related to its CD8 co-receptor independent, MAGE-A4-specific T cell receptor (TCR) at the Society for Immunotherapy of Cancer 35th Annual Meeting (SITC 2020) being held virtually on 9-14 November 2020. The poster will be available in the Virtual Poster Hall from 11-14 November 2020, 9:00 am - 5:00 pm EST (3:00 pm - 11:00 pm CET), Q&A sessions will be held on Wednesday, 11 November 2020, 5:15 pm - 5:45 pm EST (11:15 pm - 11:45 pm CET) and on Friday, 13 November 2020, 4:40 pm - 5:10 pm EST (10:40 pm - 11:10 pm CET).
Medigene currently has two proprietary T cell receptor-modified T cells (TCR-Ts) in clinical development (MDG1011 against the antigen PRAME in blood cancers and MDG1021 against the antigen HA-1 in blood cancers after stem cell transplantation). In parallel, Medigene has ongoing research efforts to discover TCR-Ts as part of its partnerships with bluebird bio, Inc. (bluebird bio) and Cytovant Sciences HK Limited, a biopharmaceutical company founded by Roivant Sciences.
The TCR-T against the cancer antigen MAGE-A4 is the most advanced program in collaboration with bluebird bio. This MAGE-A4-specific TCR may be different from other MAGE-A4 TCRs currently in development elsewhere as it works independently of signaling through the co-receptor CD8, which is found on so-called killer T cells. Any T cell, including helper T cells which express CD4 and not CD8, equipped with Medigene's MAGE-A4 TCR detects and kills tumor cells expressing MAGE-A4 in preclinical setting.
Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: "Our MAGE-A4-specific TCR is capable of directing the activity of TCR-T cells irrespective of the expression of the CD8 co-receptor. We show that the TCR, expressed in either CD4 helper or CD8 killer T cells, can trigger MAGE-A4-specific responses, thus providing the broadest array of T cell activity following encounter with MAGE-A4-positive tumor cells and the best control of tumor growth in vivo. Our allogeneic T cell priming and selection technology used to isolate this TCR is well suited to finding such non-mutated, high avidity TCRs specific for different cancer antigens which we believe form the basis of an important approach for developing next generation TCR-T cells."
The poster 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", describes the extensive preclinical characterization and assessment of the safety and potency of the MAGE-A4-specific TCR.
The MAGE-A4-specific HLA-A2-restricted TCR was isolated using an allogeneic priming technology and T cells from an HLA-A2-negative donor. The TCR was demonstrated preclinically to have a favorable safety profile and superior in vivo potency compared to TCRs isolated from an HLA-A2-positive donor (bearing a tolerized T cell repertoire to self-antigens). This non-mutated high avidity TCR was also CD8 co-receptor-independent, allowing effector functions to be elicited in CD4 helper T cells. 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.
The poster will be available at www.medigene.com/technologies/abstracts from 11 November 2020, 9:00 am EST (3:00 pm CET).
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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 first Phase I/II clinical trial of its TCR-T candidate MDG1011 in the blood cancer indications AML and MDS as well as a second Phase I clinical trial of MDG1021 in patients suffering from relapsed or persistent blood cancer after allogeneic (non-self) hematopoietic stem cell transplantation (allo-HSCT). 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.