Medigene AG: Medigene and academic partners publish a method to enhance adoptive T-cell therapies

Article in "Cancer Research" published in collaboration with scientists from nine academic research groups in Berlin, Munich and Heidelberg

Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) announces that a scientific article on a method to enhance adoptive T cell therapies has been published in the current issue of "Cancer Research" (AACR Publication: DOI: 10.1158/0008-5472.CAN-16-1922). The research results show how adoptive T cell therapies can be improved by optimizing the T cells' effector functions without changing their specificity.

Inherent intermediate-to-low avidity T-cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. The researchers demonstrated in the now published article that complementing low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen by co-expression of a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity.

Prof. Dr. Elfriede Nössner, Head of Immunoanalytics - Research Group Tissue Control of Immunocytes and Core Facility at the Helmholtz Zentrum München, and senior author of the publication, explains: "Enhanced T cells combined with checkpoint blockade might be a beneficial combination for therapeutic strategies. Altogether, the supportive effects of adding PD-1:28 to T-cell function makes it an attractive tool for adoptive T-cell therapy."

Prof. Dr. Dolores J. Schendel, CEO and CSO of Medigene AG and co-author of the publication, adds: "Upgrading the function of low-avidity T cells without changing the TCR affinity will allow a large arsenal of low-avidity T cells previously thought to be therapeutically inefficient to be considered for adoptive T-cell therapy. We are actively considering these results within Medigene for the development of future TCR therapies and are excited about the prospects of this approach"

The article entitled "Chimeric PD-1:28 receptor upgrades low-avidity T cells and restores effector function of tumor-infiltrating lymphocytes for adoptive cell therapy" can be found here online: http://cancerres.aacrjournals.org/content/early/2017/05/20/0008-5472.CAN-16-1922

The results have been generated in a research alliance of scientists from nine German academic institutions and scientists from Medigene AG.

About Medigene's TCR technology: The TCR 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 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 preparing the clinical development of its first TCR candidates and is establishing a pipeline of recombinant T-cell receptors, and has established Good Manufacturing Practice (GMP)-compliant processes for their combination with patient-derived T cells.

Medigene's first TCR immunotherapy "MDG1011" will be tested in a clinical phase I/II trial scheduled to be started by the end of 2017.