Cancer immunotherapy has been demonstrated to be highly effective by the application of immune checkpoint inhibitors as well as cellular therapies, based on adoptive transfer of T cells transgenic for chimeric antibody receptors. The latter approach is most effective in hematological malignancies, whereas results in solid tumors are less promising. The adoptive transfer of T cells targeting neoantigens by neoantigen-specific T-cell receptors (TCR) is becoming increasingly achievable with the advances in high-throughput technologies. We have previously identified mutated peptide ligands by mass spectrometry (MS) in patients with melanoma and validated several as neoantigens. We have isolated seven neoantigen-specific TCR recognizing three diverse neoantigens from one patient, demonstrating high specificity as well as tumor reactivity. Recently, we have further optimized our neoantigen discovery pipeline in a cross disease approach resulting in an substantial increase of hits and we were successful in identifying such MS-defined neoantigens in the vast majority of patients. Currently, we are developing translational strategies to prepare an early clinical trial. In addition, we are working on translational immuno-imaging strategies to track tumor-reactive T cells in vivo.
 
Angela Krackhardt is Professor of Translational Immunotherapy and senior physician at the department of Hematology and Oncology at the III.
 
Looking forward to seeing you all there!