Wang Rong-Fu, Wang Helen Y
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Cell Res. 2017 Jan;27(1):11-37. doi: 10.1038/cr.2016.155. Epub 2016 Dec 27.
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer. Current success of cancer immunotherapy is built upon the work of cancer antigens and co-inhibitory signaling molecules identified 20 years ago. Among the large numbers of target antigens, CD19 is the best target for CAR T cell therapy for blood cancer, but CAR-engineered T cell immunotherapy does not yet work in solid cancer. NY-ESO-1 is one of the best targets for TCR-based immunotherapy in solid cancer. Despite the great success of checkpoint blockade therapy, more than 50% of cancer patients fail to respond to blockade therapy. The advent of new technologies such as next-generation sequencing has enhanced our ability to search for new immune targets in onco-immunology and accelerated the development of immunotherapy with potentially broader coverage of cancer patients. In this review, we will discuss the recent progresses of cancer immunotherapy and novel strategies in the identification of new immune targets and mutation-derived antigens (neoantigens) for cancer immunotherapy and immunoprecision medicine.
利用免疫系统根除恶性细胞正成为一种极具潜力的癌症治疗新方法。美国食品药品监督管理局（FDA）批准了基于免疫疗法的药物，如西普列姆肽（Provenge）、伊匹单抗（Yervoy，抗CTLA - 4），以及最近批准的程序性细胞死亡（PD）-1抗体（帕博利珠单抗，可瑞达）用于治疗多种类型的癌症，这极大地推动了癌症免疫治疗领域的研究和临床研究。此外，最近使用NY - ESO - 1特异性T细胞受体（TCR）或CD19嵌合抗原受体（CAR）的临床试验，已在转移性癌症患者中显示出有前景的临床结果。目前癌症免疫治疗的成功建立在20年前确定的癌症抗原和共抑制信号分子的研究基础之上。在大量的靶抗原中，CD19是血液癌症CAR T细胞治疗的最佳靶点，但CAR工程化T细胞免疫疗法在实体癌中尚未起效。NY - ESO - 1是实体癌基于TCR免疫疗法的最佳靶点之一。尽管检查点阻断疗法取得了巨大成功，但仍有超过50%的癌症患者对阻断疗法无反应。新一代测序等新技术的出现增强了我们在肿瘤免疫学中寻找新免疫靶点的能力，并加速了免疫疗法的发展，有望覆盖更多癌症患者。在这篇综述中，我们将讨论癌症免疫治疗的最新进展，以及在识别用于癌症免疫治疗和免疫精准医学的新免疫靶点和突变衍生抗原（新抗原）方面的新策略。
