New data presented at AACR shows enhanced T cell functionality of MDG1015 in solid tumors

New data presented at AACR shows enhanced T cell functionality of MDG1015 in solid tumors 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 NYESO-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 Interferonγ 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 preclinical 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.”