Summary

The group works in the field of cancer immunology. We focus on the development of cancer models that better resemble human cancer, the role of the tumor stroma for tumor progression and as target for immunotherapy, and the development of strategies for convenient and effective T-cell therapy. For clinical application, we employ T cell receptor (TCR) gene therapy. We developed humanized TCRab gene loci/MHC (HLA-A2 or HLA-DR4) mice that allow isolation of human TCRs against tumor-associated antigens such as cancer-testis (CT) antigens from the non-tolerant repertoire. TCRs derived from these mice are restricted for self-MHC molecules and recognize the human self-antigen as foreign. Thus, T cells expressing such TCR resemble those that naturally protect us from pathogens; this is why we think they have an “optimal” affinity. We pioneered isolation of TCRs from the (immunized) humanized mice for HLA-A2-restricted epitopes of MAGE-A1 and NY-ESO-1, two CT antigens. Currently, we prepare the first TCR gene therapy trial with the MAGE-A1-specific TCR for treatment of Multiple Myeloma. We also isolate TCR against recurrent somatic mutations creating neoantigens.