Medigene AG, a clinical stage immune-oncology company focusing on the development of T cell immuno-therapies for the treatment of cancer, announces the grant of US patent US9,341,617B2. The patent, with an expected life-span until 2030, claims a method for the identification of antigens recognized by CD4+ T cells, including tumor infiltrating CD4+ T cells.

This patent expands Medigene's T-cell receptor (TCR) platform technology with an additional fast and efficient method for the direct identification of antigens and respective epitopes recognized by CD4+ tumor infiltrating lymphocytes and opens the way to identify immune relevant patient-specific neoantigens. Rapid definition of epitopes recognized by CD4+ T helper cells for generation of tumor vaccines also becomes potentially possible.

Prof. Dolores Schendel, CEO and CSO of Medigene, explains: "This newly patented method provides the company with a potential additional source for new TCR candidates and also allows us to identify patient-specific neoantigens seen by CD4+ T cells. While CD4+ tumor infiltrating T cells have been known in the past, finding the antigens for which these T cells are specific was very time-consuming and complex. With the covered method we are now able to overcome these problems and it helps us to provide expanded options for adoptive T-cell therapies with transgenic T-cell receptors."

Medigene holds an exclusive license to the patent that was issued to Helmholtz Zentrum München (German Research Center for Environmental Health). Patents within the same patent family have already been granted in Europe, Australia and Canada.

About Medigene's TCR patent portfolio: Medigene's IP-portfolio relating to the TCR platform comprises 4 patent families covering methods for the identification of tumor-antigen specific T cell receptors and T cell receptors targeting specific tumor antigens. The 4 patent families in turn comprise 47 granted patents (including validations in Europe) and 14 pending applications. In addition, Medigene is constantly expanding its IP portfolio by filing applications for new methods and newly identified T-cell receptors specific for various tumor-antigens.

Recent advances in cellular immunotherapy show that cancer cells can be efficiently eliminated by adoptive transfer of modified patient T cells. The main effector functions can be provided by genetically engineered lymphocytes expressing T-cell receptors isolated from tumor antigen-specific cytotoxic CD8+ lymphocytes, which recognize tumor-associated antigens presented on HLA class I molecules. Nevertheless, CD4+ T lymphocytes play a critical role for efficient and sustained cytotoxic CD8+ T cell responses and memory function. Multifunctional CD4+ T cells are essential to activate, control and maintain immune responses. CD4+ T cells recognize antigens presented on HLA class II molecules; thereby HLA class II tumor antigen-positive cells may be efficiently eliminated also by direct CD4+ cytotoxic mechanisms. It was demonstrated that adoptive transfer of tumor antigen-specific CD4+ T cells alone can lead to substantial regression of epithelial tumors (Science. 2014 May 9;344(6184):641-5).

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). A large number of specific T cells to fight the tumor is thereby made available to patients within a short period of time.

Medigene's technology for T-cell receptor-modified T cells is one of the company's highly innovative and complementary immunotherapy platforms for adoptive T-cell therapy. The TCR therapy is designed to treat patients with high tumor loads. Medigene is preparing the clinical development of its first TCR candidates and is developing a library of recombinant T-cell receptors. Moreover, a Good Manufacturing Practice (GMP)-compliant process for their combination with patient-derived T cells is currently being established. Medigene plans to commence its first own clinical TCR trials in 2017 and a second in 2018.