Summary

T-cell-based immunotherapeutic strategies for tumor patients

T cells are powerful components of the specific antitumor immune response. CD8+ cytotoxic T lymphocytes (CTLs) efficiently destroy tumor cells. CD4+ T cells improve the antigen-presenting capacity of dendritic cells (DCs) and promote the expansion and activation of tumor-reactive CTLs. Clinical trials focusing on the adoptive transfer of non-modified T cells revealed tumor regression in tumor patients. Novel T-cell-based strategies comprise the generation of T-cell receptor- or chimeric antigen receptor-engineered T cells targeting tumor-associated antigens (TAAs). The administration of such modified T cells into tumor patients also resulted in objective responses.
One major goal of our group is the identification of TAAs and derived peptide motifs that can serve as target structures for T cells. In this context, we are interested in proteins that are preferentially or specifically expressed in tumor cells and play an important role in tumor pathogenesis. The amino acid sequence of the proteins is screened for peptides predicted to bind to frequent human leukocyte antigen (HLA) molecules by using HLA-binding prediction online-tools. To evaluate the suitability of the selected peptides, specific CD8+ T-cell clones are generated. The cytotoxic activity of the peptide-specific CD8+ T-cell clones against tumor cell lines and primary tumor cells is determined by chromium release or flow cytometry-based killing assays. In addition, we perform the immune monitoring of T-cell-based treatment modalities in mouse models and tumor patients. For this, frequency, activation status and functional properties of blood-circulating or tumor-infiltrating T cells are determined by multiparametric flow cytometry, ELISPOT analysis and immunohistochemistry.