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

黑色素瘤相关硫酸软骨素蛋白多糖(MCSP)是一种大的抗原，在大多数黑色素瘤和一些其他肿瘤的表面强烈而均匀地表达。它在功能上与黑色素瘤细胞的致癌表型有关，也在肿瘤微环境中的血管周细胞中表达。自从80年代早期发现以来，针对这种极有希望的抗原的免疫治疗一直集中在抗体而不是基于T细胞的方法上。抗独特型抗体产生了一些临床益处，其中诱导MCSP特异性T细胞似乎是至关重要的。此外，在小鼠体内接种树突状细胞已经诱导了MCSP特异性T细胞和抗肿瘤作用。为了为人类的T细胞治疗，特别是疫苗试验奠定坚实的基础，我们想要识别足够数量的相关T细胞表位，并研究不同种族的自然T细胞对MCSP的反应。我们还将通过过继转移实验来测试MCSP反应性T细胞在荷瘤小鼠中的疗效。通过我们网络的互补专业知识，这些研究是可能的。

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.