New data presented at AACR Annual Meeting demonstrates significantly enhanced anti-solid tumor effects of T cells co-expressing an optimal affinity TCR targeting NY-ESO-1 and a PD1-41BB co-stimulatory switch receptor (MDG1015)
Martinsried/Munich, April 18, 2023, Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today presents preclinical data on MDG1015, a T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1 (New York esophageal squamous cell carcinoma 1) combined with the Company’s PD1-41BB switch receptor technology at the AACR Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida. The poster presentation with the title “T cells co-expressing a highly potent NY-ESO-1-specific TCR and a chimeric PD1-41BB co-stimulatory switch receptor show a favorable polyfunctional profile for the treatment of solid tumors.” can be found on Medigene’s website at https://medigene.com/science/abstracts/.
MDG1015 is a third generation TCR-T therapy that combines a specific and sensitive TCR against NY-ESO-1, a well-characterized and validated cancer antigen expressed in multiple tumor types, with the PD1-41BB switch receptor.
The data presented in the poster demonstrates that the PD1-41BB switch receptor significantly increased the activity, functionality, and proliferation of TCR-T cells targeting a specific tumor antigen, while overcoming the immunosuppressive signals from the solid tumor microenvironment (TME). Specifically, co-expression of PD1-41BB on NY-ESO-1 TCR-T cells led to a 3-fold increase in Interferon-γ release and a higher proliferation index (~1.5-fold) after antigen encounter. Up to a 5-fold increase in polyfunctionality (the production of multiple cytokines by a T cell to provide a more effective immune response) and a 6-to-8-fold higher Polyfunctional Strength Index were demonstrated for NY-ESO-1 TCR-T cells co-expressing PD1-41BB compared to T cells expressing the NY-ESO-1 TCR alone. In addition, NY-ESO-1 TCR-T cells co-expressing PD1-41BB exhibited prolonged killing activity upon continuous stimulation with NY-ESO-1 positive tumor spheroids. Notably, TCR-dependent killing was restricted to target cells expressing both NY-ESO-1 and PD-L1. The enhanced functionality of T cells was driven by increased secretion of only effector, stimulatory and chemoattractive cytokines without a substantial increase in inflammatory cytokines, leading to a more effective immune response. The pre-clinical data showed that the Medigene’s PD1-41BB co-stimulatory switch receptor is an effective molecular tool to enhance TCR-T cell functionality and redirect the inhibitory signals from the TME, thus overcoming a major obstacle to the clinical efficacy of adoptive cell therapy against solid tumors.
“Tumors expressing PD-L1 are highly immunosuppressive and this represents one of the major challenges for the treatment of a wide variety of solid cancer types,” said Selwyn Ho, Chief Executive Officer at Medigene. “The preclinical data presented today demonstrates that our PD1-41BB switch receptor has the ability to significantly enhance the anti-tumor activity of T cells expressing an optimal affinity TCR against NY-ESO-1, whilst overcoming inhibitory signals from the solid tumor microenvironment. We look forward to future opportunities to highlight data that reinforces the strong potential of MDG1015 as we advance towards the clinic and as we make progress in our aim to create highly differentiated TCR-T therapies that can address the unmet needs of patients with solid tumors.”
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About Medigene
Medigene AG (FSE: MDG1) is a leading immuno-oncology platform company dedicated to developing T-cell therapies to effectively eliminate cancer. Its end-to-end technology platform is built on multiple proprietary product development and product enhancement technologies, and allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com
About Medigene’s End-To-End Platform
Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The platform includes multiple product enhancement technologies, (e.g. PD1-41BB Switch Receptor, Precision Pairing) and development optimization technologies (e.g. Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies.
About Medigene’s MDG1015 Program
MDG1015 is a 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1, a well-recognized and validated cancer testis antigen which is expressed in multiple tumor types. MDG1015 contains our high-avidity, NY-ESO-1 TCR combined with our proprietary PD1-41BB co-stimulatory switch receptor that blocks the PD1/PD-L1 inhibitory axis while simultaneously activating the T cell through the well described -41BB pathway further enhancing the activity and persistence of the TCR-T in the hostile tumor microenvironment (TME). MDG1015 is currently undergoing IND/CTA enabling studies.
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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