Gjerstorff Morten F, Andersen Mads H, Ditzel Henrik J
Department of Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark.
Department of Haematology, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital, Herlev, Denmark.
Oncotarget. 2015 Jun 30;6(18):15772-87. doi: 10.18632/oncotarget.4694.
Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer/testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival.
近期的进展为免疫疗法作为传统癌症治疗的补充奠定了基础。因此,需要付出巨大努力来进一步提高疗效和特异性,尤其是确定用于临床试验的最佳治疗靶点。癌胚抗原具有免疫原性、高度癌症特异性,且在多种类型的癌症中频繁表达,这使其成为癌症免疫疗法(包括癌症疫苗接种和嵌合T细胞受体的过继性T细胞转移)的有前景的候选靶点。我们目前对肿瘤免疫学和免疫逃逸的理解表明,靶向致癌抗原可能有益,这意味着鉴定具有致癌特性的癌胚抗原具有高度优先性。我们实验室和其他机构最近的研究工作提供了证据,表明许多癌胚抗原实际上具有致癌功能,包括支持生长、存活和转移。这种对癌胚抗原功能的新见解有可能带来更有效的癌症疫苗。此外,将致癌性癌胚抗原的免疫靶向与传统细胞毒性疗法或新型免疫疗法(如检查点阻断或过继性转移)相结合,是一种具有高度协同作用的方法,有可能提高患者生存率。