Departments of Medicine and Surgery and the Duke Cancer Institute, Duke University School of Medicine, MSRB Room 401, Research Drive, Box 3233, Durham, NC, 27710, USA.
Department of Medicine, Cancer Vaccine Institute, University of Washington, Seattle, WA, USA.
Target Oncol. 2021 Mar;16(2):121-152. doi: 10.1007/s11523-020-00788-w. Epub 2021 Jan 29.
There are strong biologic and preclinical rationales for the development of therapeutic cancer vaccines; however, the clinical translation of this treatment strategy has been challenging. It is now understood that many previous clinical trials of cancer vaccines used target antigens or vaccine designs that inherently lacked sufficient immunogenicity to induce clinical responses. Despite the historical track record, breakthrough advances in cancer immunobiology and vaccine technologies have supported continued interest in therapeutic cancer vaccinations, with the hope that next-generation vaccine strategies will enable patients with cancer to develop long-lasting anti-tumor immunity. There has been substantial progress identifying antigens and vaccine vectors that lead to strong and broad T cell responses, tailoring vaccine designs to achieve optimal antigen presentation, and finding combination partners employing complementary mechanisms of action (e.g., checkpoint inhibitors) to overcome the diverse methods cancer cells use to evade and suppress the immune system. Results from randomized, phase 3 studies testing therapeutic cancer vaccines based on these advances are eagerly awaited. Here, we summarize the successes and failures in the clinical development of cancer vaccines, address how this historical experience and advances in science and technology have shaped efforts to improve vaccines, and offer a clinical perspective on the future role of vaccine therapies for cancer.
治疗性癌症疫苗的发展具有强大的生物学和临床前基础；然而，这种治疗策略的临床转化一直具有挑战性。现在人们已经了解到，许多先前的癌症疫苗临床试验所使用的靶抗原或疫苗设计本身缺乏足够的免疫原性，无法诱导临床反应。尽管有历史记录，但癌症免疫生物学和疫苗技术的突破性进展支持了对治疗性癌症疫苗接种的持续关注，希望下一代疫苗策略能够使癌症患者产生持久的抗肿瘤免疫力。在确定能够引发强烈和广泛的 T 细胞反应的抗原和疫苗载体、调整疫苗设计以实现最佳抗原呈递，以及寻找互补作用机制（例如检查点抑制剂）的组合伙伴以克服癌症细胞逃避和抑制免疫系统的多种方法方面已经取得了实质性进展。正在急切等待基于这些进展的治疗性癌症疫苗的随机、3 期研究结果。在这里，我们总结了癌症疫苗临床开发的成功和失败，探讨了这些历史经验和科学技术的进步如何影响改进疫苗的努力，并从临床角度展望了癌症疫苗疗法的未来作用。
