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Development of personalized treatment and novel monitoring approaches for neoantigen-directed immunotherapies in cancer
Prof. Dr. med. Angela Krackhardt Translational Immunotherapy & Apharesis Center IIIrd Medical Department Klinikum rechts der Isar TU Munich Germany
Dr. Angela Krackhardt is Professor of Translational Immunotherapy and head of the Apharesis Center at the School of Medicine, TU Munich. As a DKTK faculty member within the Cancer Immunotherapy program Dr. Krackhardt has been focusing her research activities on tumor immunotherapy since many years with special emphasis on T-cell mediated eradication of tumor cells. This includes the identification of tumor-specific T cell epitopes, especially derived from neoantigens, and the identification and characterization of T cells and T-cell receptors (TCR) recognizing such antigens.
Neoantigens derived from mutations may represent T-cell epitopes that have the potential of being recognized by the immune system as altered self-antigens, thus providing the basis for the induction of an effective tumor specific immune response. MHC restricted neo-epitopes are not necessarily presented at high densities on the tumor cells’ surface, rendering their identification challenging.
In her recent work published in Nature Communications. Dr. Krackhardt has reported on in-depth analysis of MHC peptide ligands derived from tumor tissue samples of melanoma patients proving that not only shared tumor-associated antigens, but also tumor-specific neoantigens are presented by melanoma cells that can be identified by mass spectrometry and are clinically relevant as shown by detection of defined neoantigen-specific T-cell populations in the patient. Furthermore, phosphorylated T cell epitopes were described.
Besides using tumor specific T cells for therapeutic applications Dr. Krackhardt is interested in monitoring specific T-cell populations and especially TCR-transgenic T cells during therapy. Moreover, Dr. Krackhardt is involved in clinical trials testing immune checkpoint modulation in melanoma patients.