Lim Kue Peng, Zainal Nur Syafinaz
Cancer Immunology and Immunotherapy Research Unit, Cancer Research Malaysia, Subang Jaya, Malaysia.
Front Mol Biosci. 2021 Apr 15;8:623475. doi: 10.3389/fmolb.2021.623475. eCollection 2021.
With the regulatory approval of Provenge and Talimogene laherparepvec (T-VEC) for the treatment of metastatic prostate cancer and advanced melanoma respectively, and other promising clinical trials outcomes, cancer vaccine is gaining prominence as a cancer therapeutic agent. Cancer vaccine works to induce T cell priming, expansion, and infiltration resulting in antigen-specific cytotoxicity. Such an approach that can drive cytotoxicity within the tumor could complement the success of checkpoint inhibitors as tumors shown to have high immune cell infiltration are those that would respond well to these antibodies. With the advancements in cancer vaccine, methods to monitor and understand how cancer vaccines modify the immune milieu is under rapid development. This includes using ELISpot and intracellular staining to detect cytokine secretion by activated T cells; tetramer and CyTOF to quantitate the level of antigen specific T cells; proliferation and cell killing assay to detect the expansion of T cell and specific killing activity. More recently, T cell profiling has provided unprecedented detail on immune cell subsets and providing clues to the mechanism involved in immune activation. Here, we reviewed cancer vaccines currently in clinical trials and highlight available techniques in monitoring the clinical response in patients.
随着普罗文奇（Provenge）和塔利莫基因拉罗克韦克（Talimogene laherparepvec，T-VEC）分别获批用于治疗转移性前列腺癌和晚期黑色素瘤，以及其他一些有前景的临床试验结果，癌症疫苗作为一种癌症治疗药物正日益受到关注。癌症疫苗的作用是诱导T细胞致敏、扩增和浸润，从而产生抗原特异性细胞毒性。这种能够在肿瘤内引发细胞毒性的方法，可以补充检查点抑制剂的治疗效果，因为显示具有高免疫细胞浸润的肿瘤对这些抗体的反应良好。随着癌症疫苗的发展，监测和了解癌症疫苗如何改变免疫环境的方法也在迅速发展。这包括使用酶联免疫斑点法（ELISpot）和细胞内染色来检测活化T细胞分泌的细胞因子；使用四聚体和质谱流式细胞技术（CyTOF）来定量抗原特异性T细胞的水平；使用增殖和细胞杀伤试验来检测T细胞的扩增和特异性杀伤活性。最近，T细胞分析提供了关于免疫细胞亚群前所未有的详细信息，并为免疫激活所涉及的机制提供了线索。在此，我们综述了目前正在进行临床试验的癌症疫苗，并重点介绍了监测患者临床反应的现有技术。
