Vaccine and Cell Therapy Laboratory, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Rev Cancer. 2021 Jun;21(6):360-378. doi: 10.1038/s41568-021-00346-0. Epub 2021 Apr 27.
Therapeutic cancer vaccines have undergone a resurgence in the past decade. A better understanding of the breadth of tumour-associated antigens, the native immune response and development of novel technologies for antigen delivery has facilitated improved vaccine design. The goal of therapeutic cancer vaccines is to induce tumour regression, eradicate minimal residual disease, establish lasting antitumour memory and avoid non-specific or adverse reactions. However, tumour-induced immunosuppression and immunoresistance pose significant challenges to achieving this goal. In this Review, we deliberate on how to improve and expand the antigen repertoire for vaccines, consider developments in vaccine platforms and explore antigen-agnostic in situ vaccines. Furthermore, we summarize the reasons for failure of cancer vaccines in the past and provide an overview of various mechanisms of resistance posed by the tumour. Finally, we propose strategies for combining suitable vaccine platforms with novel immunomodulatory approaches and standard-of-care treatments for overcoming tumour resistance and enhancing clinical efficacy.
在过去十年中，治疗性癌症疫苗经历了复兴。对肿瘤相关抗原、天然免疫反应的更深入了解以及新型抗原传递技术的发展，促进了疫苗设计的改进。治疗性癌症疫苗的目标是诱导肿瘤消退、消除微小残留疾病、建立持久的抗肿瘤记忆并避免非特异性或不良反应。然而，肿瘤诱导的免疫抑制和免疫抵抗对实现这一目标构成了重大挑战。在这篇综述中，我们探讨了如何改进和扩大疫苗的抗原谱，考虑了疫苗平台的发展，并探索了抗原非依赖性原位疫苗。此外，我们总结了过去癌症疫苗失败的原因，并概述了肿瘤所带来的各种耐药机制。最后，我们提出了将合适的疫苗平台与新型免疫调节方法以及标准治疗相结合的策略，以克服肿瘤耐药性并提高临床疗效。
