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靶向新抗原以诱导针对癌症的T细胞免疫的治疗性疫苗。

Therapeutic Vaccines Targeting Neoantigens to Induce T-Cell Immunity against Cancers.

作者信息

Pao Shih-Cheng, Chu Mu-Tzu, Hung Shuen-Iu

机构信息

Cancer Vaccine & Immune Cell Therapy Core Lab, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fuxing St., Taoyuan 333, Taiwan.

Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan.

出版信息

Pharmaceutics. 2022 Apr 15;14(4):867. doi: 10.3390/pharmaceutics14040867.

Abstract

Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. Tumor neoantigens derived from accumulated genetic instability can be characterized using emerging technologies, such as high-throughput sequencing, bioinformatics, predictive algorithms, mass-spectrometry analyses, and immunogenicity validation. Neoepitopes with a higher affinity for major histocompatibility complexes can be identified and further applied to the field of cancer vaccines. Therapeutic vaccines composed of tumor lysates or cells and DNA, mRNA, or peptides of neoantigens have revoked adaptive immunity to kill cancer cells in clinical trials. Broad clinical applicability of these therapeutic cancer vaccines has emerged. In this review, we discuss recent progress in neoantigen identification and applications for cancer vaccines and the results of ongoing trials.

摘要

癌症免疫疗法已取得多项临床益处,并已成为癌症治疗中不可或缺的组成部分。靶向肿瘤特异性抗原,即所谓的新抗原,在癌症免疫疗法中起着关键作用。识别新抗原但不引发不良脱靶效应的适应性免疫T细胞,在癌症免疫疗法中已显示出高效和低副作用。源自累积遗传不稳定性的肿瘤新抗原可以使用新兴技术进行表征,如高通量测序、生物信息学、预测算法、质谱分析和免疫原性验证。可以识别对主要组织相容性复合体具有更高亲和力的新表位,并进一步应用于癌症疫苗领域。由肿瘤裂解物或细胞以及新抗原的DNA、mRNA或肽组成的治疗性疫苗在临床试验中激发了适应性免疫以杀死癌细胞。这些治疗性癌症疫苗已展现出广泛的临床适用性。在本综述中,我们讨论了新抗原鉴定和癌症疫苗应用的最新进展以及正在进行的试验结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c50/9029780/b8624dcdb93f/pharmaceutics-14-00867-g001.jpg

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