Zhao Yue, Baldin Alexey V, Isayev Orkhan, Werner Jens, Zamyatnin Andrey A, Bazhin Alexandr V
Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Vaccines (Basel). 2021 Jan 25;9(2):85. doi: 10.3390/vaccines9020085.
Unlike traditional cancer therapies, cancer vaccines (CVs) harness a high specificity of the host's immunity to kill tumor cells. CVs can train and bolster the patient's immune system to recognize and eliminate malignant cells by enhancing immune cells' identification of antigens expressed on cancer cells. Various features of antigens like immunogenicity and avidity influence the efficacy of CVs. Therefore, the choice and application of antigens play a critical role in establishing and developing CVs. Tumor-associated antigens (TAAs), a group of proteins expressed at elevated levels in tumor cells but lower levels in healthy normal cells, have been well-studied and developed in CVs. However, immunological tolerance, HLA restriction, and adverse events are major obstacles that threaten TAA-based CVs' efficacy due to the "self-protein" characteristic of TAAs. As "abnormal proteins" that are completely absent from normal cells, tumor-specific antigens (TSAs) can trigger a robust immune response against tumor cells with high specificity and without going through central tolerance, contributing to cancer vaccine development feasibility. In this review, we focus on the unique features of TAAs and TSAs and their application in vaccines, summarizing their performance in preclinical and clinical trials.
与传统癌症疗法不同,癌症疫苗(CVs)利用宿主免疫的高度特异性来杀死肿瘤细胞。癌症疫苗可以通过增强免疫细胞对癌细胞上表达的抗原的识别,来训练和增强患者的免疫系统,以识别和消除恶性细胞。抗原的各种特性,如免疫原性和亲和力,会影响癌症疫苗的疗效。因此,抗原的选择和应用在癌症疫苗的建立和开发中起着关键作用。肿瘤相关抗原(TAAs)是一类在肿瘤细胞中高表达而在健康正常细胞中低表达的蛋白质,在癌症疫苗中已得到充分研究和开发。然而,由于肿瘤相关抗原的“自身蛋白”特性,免疫耐受、HLA限制和不良事件是威胁基于肿瘤相关抗原的癌症疫苗疗效的主要障碍。作为正常细胞中完全不存在的“异常蛋白”,肿瘤特异性抗原(TSAs)可以引发针对肿瘤细胞的强大免疫反应,具有高度特异性且无需经过中枢耐受,这为癌症疫苗的开发提供了可行性。在这篇综述中,我们重点关注肿瘤相关抗原和肿瘤特异性抗原的独特特征及其在疫苗中的应用,总结它们在临床前和临床试验中的表现。