TCR immunotherapy uses T cells modified to express new TCRs to enable detection and killing of cancer cells. Efficacy of TCR immunotherapy depends on targeting antigenic peptides that are efficiently presented by the best suited major histocompatibility complex (MHC) molecules of cancer cells. However, efficient strategies are lacking to easily identify TCRs recognizing immunodominant peptide-MHC (pMHC) combinations utilizing any of the six possible MHC class I alleles of a cancer cell. The researchers generated a MHC cell library and developed an approach to detect, isolate and re-express TCRs specific for immunodominant pMHCs. This was applied to identify a human papillomavirus (HPV16) oncogene E5-specific TCR, recognizing a novel, naturally processed pMHC (HLA-B*15:01), and a cytomegalovirus-specific TCR targeting an immunodominant pMHC (HLA-B*07:02).
Prof. Dr. Wolfgang Uckert, Head of the group for Molecular Cell Biology and Gene Therapy at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, and senior author of the publication, explains: "These exciting results show that our approach provides a useful tool to isolate TCRs specific for novel and immunodominant pMHC targets in an unbiased manner that can be used in future TCR immunotherapies against virus targets."
Prof. Dr. Dolores J. Schendel, CEO and CSO of Medigene AG and co-author of the publication, adds: "Although Medigene currently has no immediate plans for clinical application of TCRs targeting viral antigens, the proof of concept results of this study further extend technologies for efficient identification of TCRs of diverse specificity, including those for important viral pathogens."
The article entitled "Unbiased identification of T cell receptors targeting immunodominant peptide-MHC complexes for T cell receptor immunotherapy" can be found here online: http://online.liebertpub.com/doi/pdf/10.1089/hum.2017.122
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.
Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.
For more information, please visit http://www.medigene.com
This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.
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