Medigene AG 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. 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 receptors. The data presented in the poster demonstrates that the PD1-41BB switches 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-? 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-1TCR-T cells co-expressing PD1-41BB compared to T cells expressing the NY-ESO-1 tCR alone.

In addition, NY-ESO-1TCR-T cells co-expressed 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 attractive 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.