Targeting invasiveness-inducing Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP) as a new target antigen for specific immunotherapy

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Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP) is a large antigen strongly and uniformly expressed on the surface of most melanomas as well as some other tumors. It is functionally relevant for the oncogenic phenotype of melanoma cells, and is also expressed by pericytes of blood vessels in the tumor microenvironment. Since its discovery in the early eighties immunotherapies targeting this highly promising antigen due to its surface expression have focused on antibody- rather than T cell-based approaches. Anti-idiotypic antibodies produced some clinical benefit for which induced MCSP-specific T cells appeared crucial. Furthermore, vaccination with dendritic cells in mice has induced MCSP-specific T cells and anti-tumor effects. To set a solid stage for a T cell-based therapy in man, notably a vaccination trial, we want to identify a sufficient number of relevant T-cell epitopes and to study the natural T cell response to MCSP in different ethnicities. We will also test the efficacy of MCSP-reactive T cells by adoptive transfer experiments in tumor-bearing mice. The studies are possible by the complementary expertise of our network.