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聚糖（MCSP）是一种在大多数黑色素瘤以及一些其他肿瘤表面强烈且均匀表达的大抗原。它在功能上与黑色素瘤细胞的致癌表型相关，并且也由肿瘤微环境中的血管周细胞表达。自八十年代早期发现以来，由于其表面表达，靶向这种非常有前途的抗原的免疫疗法一直专注于基于抗体而不是T细胞的方法。抗独特型抗体产生了一些临床益处，其中诱导的MCSP特异性T细胞显得至关重要。此外，在小鼠中接种树突状细胞诱导MCSP特异性T细胞和抗肿瘤作用。为了为人类基于T细胞的治疗，特别是疫苗接种试验奠定坚实的基础，我们希望确定足够数量的相关T细胞表位，并研究不同种族中对MCSP的天然T细胞应答。我们还将在荷瘤小鼠中通过过继转移实验测试MCSP反应性T细胞的功效。这些研究是可能的补充专业知识，我们的网络。

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.