In recent years the breakthrough clinical success of T-cell based immunotherapy approaches including advances in allogeneic stem cell transplantation, checkpoint inhibitors, CAR T cells, bispecific antibodies and adoptive T-cell transfer have revolutionized treatment of several malignancies. However, still some patients do not respond to available therapeutic strategies at all, others for limited time only. Remaining challenges to augment efficacy of T cell-based immunotherapy are particularly to improve specificity and increase the frequency of anti-tumor immune responses, to reduce toxicity and to expand the spectrum of targetable cancer entities. A rational and promising approach to achieve this goal is peptide-based immunotherapy, which represents a low side-effect approach relying on specific immune recognition of tumor-associated HLA (human leucocyte antigen) presented peptides.
Our research group works on the direct mass spectrometric analysis of these HLA presented peptides, the so called immunopeptidome of different tumors with the aim to (I) identify and characterize novel tumor-associated HLA-presented antigens, to (II) evaluate the influence of different cancer drugs on the immunopeptidome of tumor cells and to (III) translate these experimental results in a final step into clinical peptide-based immunotherapy concepts for cancer patients. For chronic lymphocytic leukemia (CLL) this goal has already been achieved: The first multicenter patient-individualized peptide vaccination study for the treatment of CLL patients (iVAC-CLL01, NCT02802943) has been established and is successfully recruiting since October 2016.