Department of Surgery, Washington University School of Medicine, St Louis.
The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St Louis, USA.
Ann Oncol. 2017 Dec 1;28(suppl_12):xii11-xii17. doi: 10.1093/annonc/mdx681.
Cancer neoantigens are antigens that result from somatic mutations present in individual cancers. Neoantigens are considered important targets for cancer immunotherapy because of their immunogenicity and lack of expression in normal tissues. Next-generation sequencing technologies and computational analysis have recently made neoantigen discovery possible. Although neoantigens are important targets of checkpoint blockade therapy, neoantigen vaccines are currently being investigated in preclinical models and early-phase human clinical trials. Preliminary results from these clinical trials demonstrate that dendritic cell, synthetic long peptide, and RNA-based neoantigen vaccines are safe, and capable of inducing both CD8+ and CD4+ neoantigen-specific T-cell responses. We and others are testing neoantigen vaccines in melanoma, breast cancer, non-small-cell lung cancer and other cancer types. Since cancers have evolved mechanisms to escape immune control, it is particularly important to study the efficacy of neoantigen vaccines in combination with other immunotherapies including checkpoint blockade therapy, and immune therapies targeting the immunosuppressive tumor microenvironment.
癌症新生抗原是指个体癌症中存在的体细胞突变所产生的抗原。由于其免疫原性和在正常组织中缺乏表达，新生抗原被认为是癌症免疫治疗的重要靶点。新一代测序技术和计算分析最近使得新生抗原的发现成为可能。尽管新生抗原是检查点阻断治疗的重要靶点，但新生抗原疫苗目前正在临床前模型和早期人体临床试验中进行研究。这些临床试验的初步结果表明，树突状细胞、合成长肽和基于 RNA 的新生抗原疫苗是安全的，能够诱导 CD8+和 CD4+ 新生抗原特异性 T 细胞反应。我们和其他人正在黑色素瘤、乳腺癌、非小细胞肺癌和其他癌症类型中测试新生抗原疫苗。由于癌症已经进化出逃避免疫控制的机制，因此研究新生抗原疫苗与其他免疫疗法（包括检查点阻断疗法和针对免疫抑制肿瘤微环境的免疫疗法）联合使用的疗效尤为重要。
