Medigene’s PD1-41BB switch receptor effectively enhances TCR-T cells to fight solid tumors

Planegg/Martinsried – 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 pre-clinical research results focusing on its PD1-41BB switch receptor technology in a poster to be presented at the Society for Immunotherapy of Cancer 35th Annual Meeting (SITC 2020) being held virtually on 9-14 November 2020. The poster # 614 will be available in the Virtual Poster Hall from 11-14 November 2020 from 9:00 am – 5:00 pm EST (3:00 pm – 11:00 pm CET), Q&A sessions will be held on Thursday, 12 November 2020, 4:50 pm – 5:20 pm EST (10:50 pm – 11:20 pm CET) and on Saturday, 14 November 2020, 1:00 pm – 1:30 pm EST (7:00 pm – 7:30 pm CET).

The poster # 614 entitled, “Co-stimulation via PD1-41BB chimeric switch receptor enhances function of TCR-T cells in an immune-suppressive milieu and under chronic antigen stimulation”, describes 2- and 3-dimensional in vitro tumor cell culture models representing the harsh conditions encountered by T cells in solid tumors including low nutrients and high levels of immunosuppressive soluble factors. T cell receptor-modified T cells (TCR-Ts) which also express Medigene’s PD1-41BB switch receptor have the ability to overcome the inhibitory tumor microenvironment and repeatedly kill tumor cells in multiple challenges. The PD1-41BB expressing TCR-T cells show a higher level of metabolic fitness enabling them to persist and proliferate much more effectively despite the normally negative factors produced by tumor cells.

Further research including in vivo studies and safety evaluations will be conducted towards eventual clinical trials of PD1-41BB-expressing TCR-T cells in the therapeutic treatment of solid tumors.

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: “In preclinical studies we have shown that our PD1-41BB switch receptor significantly enhances the functionality of TCR-Ts in a hostile solid tumor microenvironment. Enabling our TCR-Ts to function with greater activity in the solid tumor setting, which normally shuts T cells down, should give our TCR-Ts the ability to persist longer and hopefully bring about durable therapeutic responses in the clinic.”

The poster will be available at from 11 November 2020, 9:00 am EST (3:00 pm CET).

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About Medigene
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.
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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.

About Medigene’s PD1-41BB switch receptor
Checkpoint inhibition via PD1-PDL1 pathway: Solid tumor cells are known to be sensitive to killing by activated T cells. Tumor cells can escape this killing activity by expressing inhibitory molecules, so-called ‘checkpoint proteins’, such as Programmed Death Ligand 1 (PD-L1) on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 by tumors represents an adaptive immune resistance mechanism that can lead to tumor survival and growth.

The 4-1BB co-stimulatory signaling pathway: Effective T cell immune responses to antigens typically require costimulatory signals to be received alongside the primary antigenic stimulation via the T cell receptor (TCR). The intracellular signaling domains of the 4-1BB protein offer a well-characterized pathway to positively enhance T cell responses.

Medigene’s PD1-41BB switch receptor takes advantage of the binding of PD-1 on the T cells to PD-L1 on tumors. In the switch receptor, the inhibitory signaling domain of PD-1 has been substituted with the activating signaling domain of 4-1BB. As a result, the switch receptor then delivers an activating signal to the TCR-T cells (not the usual inhibitory signal of PD-1). This enables the PD1-41BB-modified TCR-T cells to proliferate strongly in the presence of PD-L1-positive tumor cells and to mediate greater killing of tumor cells upon repeated exposure. Additionally, signals mediated through the switch receptor also enhance metabolic fitness of TCR-T cells, enabling better function in conditions of low levels of glucose or high levels of the immunosuppressive factor TGFß, two conditions that are characteristic of strongly hostile tumor microenvironments.

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.

Dr. Gary Waanders, Dr. Anna Niedl
Phone: +49 89 2000 3333 01

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