a Medical Oncology Unit , San Gerardo Hospital , Monza , Italy.
b Department of Surgery , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.
Expert Opin Biol Ther. 2018 Jul;18(7):765-784. doi: 10.1080/14712598.2018.1485649. Epub 2018 Jun 17.
Cancer vaccines represent one of the oldest immunotherapy strategies. A variety of tumor-associated antigens have been exploited to investigate their immunogenicity as well as multiple strategies for vaccine administration. These efforts have led to the development of several clinical trials in tumors with different histological origins to test the clinical efficacy of cancer vaccines. However, suboptimal clinical results have been reported mainly due to the lack of optimized strategies to induce strong and sustained systemic tumor antigen-specific immune responses.
We provide an overview of different types of cancer vaccines that have been developed and used in the context of clinical studies. Moreover, we review different preclinical and clinical strategies pursued to enhance the immunogenicity, stability, and targeting at tumor site of cancer vaccines.
Additional and appropriate preclinical studies are warranted to optimize the immunogenicity and delivery of cancer vaccines. The appropriate choice of target antigens is challenging; however, the exploitation of neoantigens generated from somatic mutations of tumor cells represents a promising approach to target highly immunogenic tumor-specific antigens. Remarkably, the investigation of the combination of cancer vaccines with immunomodulating agents able to skew the tumor microenvironment from immunosuppressive to immunostimulating will dramatically improve their clinical efficacy.
癌症疫苗是最古老的免疫疗法策略之一。已经开发了多种肿瘤相关抗原来研究它们的免疫原性，以及多种疫苗接种策略。这些努力导致了针对不同组织起源的肿瘤的临床试验的发展，以测试癌症疫苗的临床疗效。然而，由于缺乏优化的策略来诱导强烈和持久的全身肿瘤抗原特异性免疫反应，报道的临床结果并不理想。
我们提供了已开发并在临床研究背景下使用的不同类型癌症疫苗的概述。此外，我们回顾了为提高癌症疫苗的免疫原性、稳定性和肿瘤部位靶向性而采用的不同临床前和临床策略。
需要进行额外和适当的临床前研究，以优化癌症疫苗的免疫原性和递送。选择合适的靶抗原具有挑战性；然而，利用来自肿瘤细胞体细胞突变产生的新抗原代表了靶向高度免疫原性肿瘤特异性抗原的一种有前途的方法。值得注意的是，研究癌症疫苗与能够将肿瘤微环境从免疫抑制转变为免疫刺激的免疫调节药物的联合应用将极大地提高其临床疗效。
