Supabphol Suangson, Li Lijin, Goedegebuure S Peter, Gillanders William E
Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
The Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Expert Opin Investig Drugs. 2021 May;30(5):529-541. doi: 10.1080/13543784.2021.1896702. Epub 2021 Mar 31.
Derived from genetic alterations, cancer neoantigens are proteins with novel amino acid sequences that can be recognized by the immune system. Recent evidence demonstrates that cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity, while minimizing the potential for autoimmune toxicity. Advances in sequencing technologies, neoantigen prediction ?algorithms,? and other technologies have dramatically improved the ability to identify and prioritize cancer neoantigens. These advances have generated considerable enthusiasm for ?the ?development of neoantigen vaccines. Several neoantigen vaccine platforms are currently being evaluated in early phase clinical trials including the synthetic long peptide (SLP), RNA, dendritic cell (DC), and DNA vaccine platforms.
In this review, we describe, evaluate the mechanism(s) of action, compare the advantages and disadvantages, and summarize early clinical experience with each vaccine platform. We provide perspectives on the future directions of the neoantigen vaccine field. All data are derived from PubMed and ClinicalTrials search updated in October 2020.
Although the initial clinical experience is promising, significant challenges to the success of neoantigen vaccines include limitations in neoantigen identification and the need to successfully target the immunosuppressive tumor microenvironment.
癌症新抗原源自基因改变，是具有可被免疫系统识别的新氨基酸序列的蛋白质。最近的证据表明，癌症新抗原是癌症免疫疗法的重要靶点。癌症新抗原疫苗的目标是诱导新抗原特异性免疫反应和抗肿瘤免疫力，同时将自身免疫毒性的可能性降至最低。测序技术、新抗原预测算法及其他技术的进步极大地提高了识别癌症新抗原并对其进行优先级排序的能力。这些进展激发了人们对开发新抗原疫苗的极大热情。目前有几种新抗原疫苗平台正在早期临床试验中进行评估，包括合成长肽（SLP）、RNA、树突状细胞（DC）和DNA疫苗平台。
在本综述中，我们描述、评估各疫苗平台的作用机制，比较其优缺点，并总结早期临床经验。我们对新抗原疫苗领域的未来方向提供了观点。所有数据均来自2020年10月更新的PubMed和ClinicalTrials搜索。
尽管初步临床经验令人鼓舞，但新抗原疫苗成功面临的重大挑战包括新抗原识别的局限性以及成功靶向免疫抑制性肿瘤微环境的必要性。
