Feola Sara, Chiaro Jacopo, Martins Beatriz, Cerullo Vincenzo
Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, 00790 Helsinki, Finland.
Helsinki Institute of Life Science (HiLIFE), Fabianinkatu 33, University of Helsinki, 00710 Helsinki, Finland.
Cancers (Basel). 2020 Jun 23;12(6):1660. doi: 10.3390/cancers12061660.
According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.
根据最新可得数据，癌症是第二大致死原因，这凸显了新型癌症治疗方法的必要性。在此背景下，免疫疗法正成为许多癌症，尤其是转移性黑色素瘤可靠的一线治疗方法。事实上，在针对免疫检查点分子（如PD-1、PD-L1和CTLA-4）的抗体近期获得临床批准后，癌症免疫疗法引起了极大关注，这些抗体解除了免疫系统的制动，从而复兴了一个原本研究较少的领域。癌症免疫疗法主要依赖于肿瘤微环境（TME）中细胞毒性CD8 T淋巴细胞（CTL）的产生和刺激，启动T细胞并建立高效持久的抗肿瘤免疫力。因此，明确和鉴定用于治疗性癌症疫苗的免疫原性T细胞表位显然很有必要。肿瘤表面人类白细胞抗原-1（HLA-I）复合物中天然呈递的抗原是引发特异性抗肿瘤CD8+ T细胞反应的主要因素。然而，其鉴定方法一直是可靠表征它们的主要瓶颈。因此，抗原发现领域仍有待改进。本综述旨在定义当今所谓的肿瘤抗原，主要关注CTL抗原肽。我们还回顾了迄今为止开发和应用的抗原发现技术，探讨了HLA-I肽的直接洗脱和表位的计算机预测。最后，综述的最后一部分分析了抗原发现领域未来的挑战和方向。
