由于其便捷性和对肿瘤抗原的定向作用，原位免疫疫苗接种是癌症免疫治疗中一种理想的策略。本研究设计了一种基于阳离子肽、带有胆固醇修饰的DP7-C的原位纳米疫苗，用于癌症免疫治疗，并成功研发了这种易于制备的癌症纳米疫苗。该纳米疫苗包含混合的小干扰RNA（siRNA）和免疫佐剂CpG ODNs，在癌症治疗中具有协同作用。该纳米疫苗能够诱导肿瘤细胞死亡，促进抗原呈递，并在肿瘤微环境（TME）中缓解免疫抑制。此外，该纳米疫苗被用于CT26（热性肿瘤）和B16F10（冷性肿瘤）肿瘤模型小鼠中，靶向原发肿瘤并诱导系统性抗肿瘤免疫，抑制了转移。验证了该纳米疫苗可以将冷性肿瘤转化为热性肿瘤。此外，该纳米疫苗通过调节TME，增强了CT26和B16F10肿瘤携带小鼠对抗PD-1治疗的免疫反应。这种包含siRNA混合物/CpG ODN/自组装肽的纳米疫苗是一种简单、通用的工具，能够有效产生特异性肿瘤细胞抗原，并能与免疫肿瘤学药物结合，增强抗肿瘤免疫活性。这种多功能方法为开发癌症纳米疫苗提供了一种替代途径。© 2023年施普林格自然出版集团出版的《先进科学》。

In situ vaccination is a desirable strategy for cancer immunotherapy due to its convenience and capacity to target tumor antigens. Here, an in situ nanovaccine based on a cationic peptide with cholesterol-modified, DP7-C, for cancer immunotherapy is rationally designed, and developed a cancer nanovaccine that is easy to preparate. The nanovaccine includes cocktail small interfering RNAs (siRNAs) and immunologic adjuvant CpG ODNs, has synergistic effect in the cancer treatment. This nanovaccine can induce tumor cell death, promote antigen presentation and relieve immune suppression in the tumor microenvironment (TME). Moreover, this nanovaccine is administered to CT26 (hot) and B16F10 (cold) tumor model mice, in which it targeted the primary tumors and induced systemic antitumor immunity to inhibit metastasis. It is validated that the nanovaccine can convert cold tumors into hot tumors. Furthermore, the nanovaccine increased the immune response to anti-PD-1 therapy by modulating the TME in both CT26- and B16F10-tumor-bearing mice. The siRNA cocktail/CpG ODN/self-assembling peptide nanovaccine is a simple and universal tool that can effectively generate specific tumor cell antigens and can be combined with immuno-oncology agents to enhance antitumor immune activity. The versatile methodology provides an alternative approach for developing cancer nanovaccines.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.