Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Expert Rev Vaccines. 2020 Feb;19(2):163-173. doi: 10.1080/14760584.2020.1733420. Epub 2020 Mar 14.
: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.
KRAS 突变是多种癌症的遗传驱动因素，在过去 30 年中一直挑战着临床抗癌治疗。KRAS 突变编码的新抗原被鉴定为具有高免疫原性的肿瘤特异性抗原，可用于递送精准癌症疫苗以促进抗肿瘤免疫反应。基于 KRAS 突变的癌症疫苗已产生令人鼓舞的临床前和临床结果。癌症疫苗是治疗 KRAS 驱动型癌症的一种很有前途的方法。在这篇综述中，我们总结了针对 KRAS 的疫苗的开发和进展，并评估了它们在当前 KRAS 驱动型癌症治疗领域中的潜在益处和障碍。基于 KRAS 突变的癌症疫苗可以在 KRAS 驱动型癌症患者中诱导免疫原性。然而，肿瘤微环境中的细胞和分子因素等抑制肿瘤的机制可能会限制疫苗的疗效。将 KRAS 驱动的治疗性癌症疫苗与其他方法和佐剂相结合，可以克服免疫抑制并促进治疗成功。
