Department of NanoEngineering, University of California , San Diego, CA, USA.
Program in Chemical Engineering, University of California , San Diego, CA, USA.
Expert Opin Drug Discov. 2021 Jan;16(1):89-99. doi: 10.1080/17460441.2020.1811673. Epub 2020 Aug 31.
Breakthroughs in cancer immunotherapy have spurred interest in the development of vaccines to mediate prophylactic protection and therapeutic efficacy against primary tumors or to prevent relapse. However, immunosuppressive mechanisms employed by cancer cells to generate effective resistance have hampered clinical translation of therapeutic cancer vaccines. To enhance vaccine efficacy, the immunomodulatory properties of cytoreductive therapies could amplify a cancer-specific immune response.
Herein, the authors discuss therapeutic cancer vaccines that harness whole cells and antigen-targeted vaccines. First, recent advancements in both autologous and allogeneic whole-cell vaccines and combinations with checkpoint blockade and chemotherapy are reviewed. Next, tumor antigen-targeted vaccines using peptide-based vaccines and DNA-vaccines are discussed. Finally, combination therapies using antigen-targeted vaccines are reviewed.
A deeper understanding of the immunostimulatory properties of cytoreductive therapies has supported their utility in combination therapies involving cancer vaccines as a potential strategy to induce a durable anti-tumor immune response for multiple types of cancers. Based on current evidence, combination therapies may have synergies that depend on the identity of the cytotoxic agent, vaccine target, dosing schedule, and cancer type. Together, these observations suggest that combining cancer vaccines with immunomodulatory cytoreductive therapy is a promising strategy for cancer therapy.
癌症免疫疗法的突破激发了人们开发疫苗的兴趣,以期对原发性肿瘤进行预防保护和治疗效果,或预防复发。然而,癌细胞用来产生有效抵抗的免疫抑制机制阻碍了治疗性癌症疫苗的临床转化。为了提高疫苗的疗效,细胞减灭疗法的免疫调节特性可以放大针对癌症的免疫反应。
本文讨论了利用全细胞和抗原靶向疫苗的治疗性癌症疫苗。首先,综述了最近在自体和同种异体全细胞疫苗方面的进展,以及与检查点阻断和化疗的联合应用。其次,讨论了使用基于肽的疫苗和 DNA 疫苗的肿瘤抗原靶向疫苗。最后,讨论了抗原靶向疫苗的联合治疗。
对细胞减灭疗法的免疫刺激特性的更深入了解支持了它们在涉及癌症疫苗的联合治疗中的应用,这是一种诱导多种癌症持久抗肿瘤免疫反应的潜在策略。基于现有证据,联合治疗可能具有协同作用,这取决于细胞毒性药物、疫苗靶点、剂量方案和癌症类型的不同。总之,这些观察结果表明,将癌症疫苗与免疫调节性细胞减灭疗法相结合是癌症治疗的一种很有前途的策略。