Medigene AG presents an overview on elevated activity of T cell receptor engineered T cell (TCR-T) therapies when combining Medigenes PD1-41BB switch receptor with T cell receptors (TCRs) targeting different antigens at the Immuno-Oncology Summit Europe June 20-22, 2023 in London, UK. The data provides an overview on the enhanced activity of TCR-T therapy seen with the combination of the PD1-41BB switch receptors with TCRs specific for different target antigens. Irrespective of the target antigen specificity, TCRs combined with the PD1-41BB switches receptor displayed superior T cell functionality in vitro and increased T cell efficacy in vivo as compared to TCR-T cells without the switch receptor ("naked" TCR).

The PD1-41BB costimulatory switch receptor is an highly innovative receptor that enhances TCR-T cell functionality, enabling it to mitigate against the immunosuppressive TME, improve efficacy as well as enable sustained immune responses. In the preclinical models, the expression of the PD1-41 BB switch receptor led to enhanced cytotoxicity and proliferative capacity of TCR-T cells surpassing the capabilities of TCR-T cells expressing the TCR alone ("naked" TCR"). Cancer cell lines exposed to the combination of TCR+PD1-41BB displayed elevated interferon-gamma (IFN) release as a survey parameter of superior TCR-T cell functionality when compared to the naked TCR.

The observed effect was restricted to cell lines expressing both the appropriate antigen and PD-L1, underpinning the specificity of the TCR in combination with the PD1-41 BB switches receptor. In presence of the PD1-41B switch receptor, enhanced TCR-T cell proliferation and elevated killing ability of 3D tumor spheroids was detected as compared to the naked TCR; Also, a stem cell-like and central memory T cells were maintanted in presence of the combination of TCR+ PD1-41BB and were comparable to the levels observed for the naked TCR. The killing efficacy of TCR-T cells in vivo was dependent on the antigen expression on tumor cells.

In presence of high levels of antigen, the naked TCR prolonged survival in vivo and attenuated tumor growth compared to cancer cellsexpression with low levels of antigen. Exposure to TCR-T cells co-expressing the combination of TCR+PD1-41BB restored the anti-tumor effects in cancer cells with low antigen levels. The combination of TCR+PD1-41BB exhibited remarkable clinical efficacy in these preclinical in vivo xenograft models, also in cancer cells displaying low levels of targetable antigen.