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Personal Neoantigen Vaccines for the Treatment of Cancer
Annual Review of Cancer Biology ( IF 4.7 ) Pub Date : 2021-03-04 , DOI: 10.1146/annurev-cancerbio-060820-111701
Keerthi Shetty 1 , Patrick A. Ott 1, 2, 3, 4
Affiliation  

Cancer vaccines can generate and amplify tumor-specific T cell responses with the promise to provide long-term control of cancer. All cancer cells harbor genetic alterations encoding neoantigens that are specific to the tumor and not present in normal tissue. Similar to foreign antigens targeted by T cells in infectious disease settings, neoantigens represent the long elusive immunogens for cancer vaccination. Since the vast majority of mutations are unique to individual tumors, neoantigen vaccines require custom design for each patient. The availability of rapid and cost-effective genome sequencing, along with advanced bioinformatics tools, now allows neoantigen-target discovery and vaccine manufacturing in sufficient time for the treatment of cancer patients. Clinical trials in melanoma and glioblastoma have demonstrated the feasibility, immunogenicity, and signals of efficacy of this personalized immunotherapy approach. Key unresolved areas include identification of the most effective vaccine delivery platforms, validation and consensus of neoantigen target selection, and optimal strategies for partnering immunotherapies. Given the universal presence of mutations in cancer and the patient-tailored paradigm, personalized neoantigen vaccines have potential applicability for all cancer patients.

中文翻译:


用于治疗癌症的个人新抗原疫苗

癌症疫苗可以产生并放大肿瘤特异性T细胞应答,有望提供对癌症的长期控制。所有癌细胞都具有编码新抗原的遗传改变,这些新抗原对肿瘤具有特异性,并且在正常组织中不存在。类似于传染性疾病中T细胞靶向的外源抗原,新抗原代表了用于癌症疫苗接种的长期难以捉摸的免疫原。由于绝大多数突变是个别肿瘤所特有的,因此新抗原疫苗需要为每位患者定制设计。快速,经济高效的基因组测序以及先进的生物信息学工具的推出,现在使新抗原靶标的发现和疫苗的生产能够在足够的时间内用于癌症患者的治疗。在黑色素瘤和胶质母细胞瘤中进行的临床试验证明了该方法的可行性,免疫原性,以及这种个性化免疫疗法方法的功效信号。尚未解决的关键领域包括最有效的疫苗输送平台的鉴定,新抗原靶标选择的确认和共识以及合作免疫疗法的最佳策略。鉴于癌症中普遍存在突变和患者量身定制的范例,个性化的新抗原疫苗对所有癌症患者都有潜在的适用性。

更新日期:2021-03-05
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