Planegg (pta003/04.01.2019/07:30) - -A mechanism expected to overcome checkpoint blockade in T cells
Medigene AG (FSE: MDG1, Prime Standard, SDAX) today announced that it has entered into an exclusive license agreement with Helmholtz Zentrum Munich (HMGU), a German public research institution operating in the field of environmental health, for a chimeric co-stimulatory receptor which is a fusion protein of PD-1 and 4-1BB. Medigene intends to explore applying the receptor in combination with Medigene's T cell receptor-modified T cells (TCR-Ts) for the treatment of solid tumors. The co-stimulator was developed by researchers at the HMGU as a strategy to potentially overcome the blockade of T cells by solid tumors.
Many solid tumors create a hostile microenvironment to inhibit immune cell attack, employing checkpoint mechanisms to emit signals that impede T cell activity. The PD-1/4-1BB molecule is designed to reverse the "stop" signal to a "go" command to help T cells overcome this checkpoint blockade.
Prof. Dolores Schendel, CEO and CSO of Medigene, comments: "Medigene believes that T cell therapy for solid tumors must include not only an optimal T cell receptor specific for the tumor, but also an additional feature to overcome T cell blockade. Gaining access to this co-stimulator gives us the exciting opportunity to improve functionality of Medigene's TCR-Ts to achieve an efficacious response against solid tumors. The licensed molecule works by inhibiting negative immune regulation, a principle that was discovered by James P. Allison and Tasuku Honjo, the importance of which was recognized with the Nobel Prize in Medicine in 2018."
Scientists from HMGU and Medigene have previously shown that low-avidity (1) T cells recognizing tumor cells can achieve comparable effector functions to those of high-avidity T cells of identical specificity through the co-expression of a chimeric co-stimulatory receptor (AACR Publication: DOI: 10.1158/0008-5472.CAN-16-1922). By binding to PD-L1/PD-L2 on the surface of tumor cells, a chimeric co-stimulatory receptor converts a normally negative, inhibitory signal into a positive signal in the T cell, thereby activating T cells instead of inactivating them.
Medigene will now evaluate preclinically the use of this chimeric co-stimulatory receptor in combination with tumor-specific TCR-Ts generated by Medigene to potentiate immune responses against solid tumors.
Prof. Dr. Elfriede Nößner, Head of Immunoanalytics at the Helmholtz Zentrum Munich, and inventor of the licensed receptor, comments: "I am excited that Medigene will explore how to implement the use of our chimeric co-stimulatory receptor with their TCR-T platform. We are convinced that Medigene's TCR technology is perfectly suited for the development of potential clinical applications to improve therapies for a variety of different solid tumor types."
Medigene is acquiring a worldwide, exclusive license for the therapeutic and diagnostic use of this chimeric co-stimulatory receptor in the field of TCR-therapy (TCR-Ts) and DC vaccines (DCs). The chimeric co-stimulatory receptor is covered by a patent application filed by HMGU in 2017 with the application number PCT/EP2017/056931. Medigene will pay HMGU an upfront fee, an annual maintenance fee, milestone payments and royalties on marketed therapeutic and diagnostic products containing the chimeric co-stimulatory receptor. Confidentiality was agreed regarding further financial details. Ascenion GmbH, the technology transfer partner of the HMGU has successfully negotiated the license agreement.
(1) Avidity: Avidity is the totality of the affinities of all receptors on a cell. Affinity is the force of a single antigen-TCR binding
About Medigene's TCR-Ts: Medigene's first TCR-T candidate, MDG1011, is in a Phase I/II clinical trial for various blood cancer indications started in 2018. The TCR-T technology aims at arming the patient's own T cells with tumor-specific T cell receptors. The receptor-modified 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). TCR-T therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy.
Medigene is establishing a pipeline of recombinant T cell receptors and has a collaboration with bluebird bio, Inc. for the development of six TCR-Ts.
Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, SDAX) 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 the focus on T cell-receptor modified T cells (TCR-Ts) and has projects currently in preclinical and clinical development.
For more information, please visit http://medigene.com
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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