Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, P. R. China.
College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, P. R. China.
Adv Mater. 2024 Oct;36(40):e2409590. doi: 10.1002/adma.202409590. Epub 2024 Aug 28.
Personalized cancer vaccines based on tumor cell lysates offer promise for cancer immunotherapy yet fail to elicit a robust therapeutic effect due to the weak immunogenicity of tumor antigens. Autophagosomes, obtained from pleural effusions and ascites of cancer patients, have been identified as abundant reservoirs of tumor neoantigens that exhibit heightened immunogenicity. However, their potential as personalized cancer vaccines have been constrained by suboptimal lymphatic-targeting performances and challenges in antigen-presenting cell endocytosis. Here,a reinforced biomimetic autophagosome-based (BAPs) nanovaccine generated by precisely amalgamating autophagosome-derived neoantigens and two types of adjuvants capable of targeting lymph nodes is developed to potently elicit antitumor immunity. The redox-responsive BAPs facilitate cytosolic vaccine opening within antigen-presenting cells, thereby exposing adjuvants and antigens to stimulate a strong immune response. BAPs evoke broad-spectrum T-cell responses, culminating in the effective eradication of 71.4% of established tumors. Notably, BAPs vaccination triggers enduring T-cell responses that confer robust protection, with 100% of mice shielded against tumor rechallenge and a significant reduction in tumor incidence by 87.5%. Furthermore, BAPs synergize with checkpoint blockade therapy to inhibit tumor growth in the poorly immunogenic breast cancer model. The biomimetic approach presents a powerful nanovaccine formula with high versatility for personalized cancer immunotherapy.
基于肿瘤细胞裂解物的个体化癌症疫苗为癌症免疫治疗带来了希望，但由于肿瘤抗原的免疫原性较弱，未能产生强大的治疗效果。从癌症患者的胸腔积液和腹水获得的自噬体已被确定为富含肿瘤新抗原的丰富储库，这些新抗原具有更高的免疫原性。然而，由于淋巴靶向性能不佳和抗原呈递细胞内吞作用的挑战，它们作为个体化癌症疫苗的潜力受到限制。在这里，通过精确融合自噬体衍生的新抗原和两种能够靶向淋巴结的佐剂，开发了一种强化的仿生自噬体基（BAPs）纳米疫苗，以有效地引发抗肿瘤免疫。氧化还原响应的 BAPs 促进抗原呈递细胞内的细胞溶质疫苗开放，从而使佐剂和抗原暴露以刺激强烈的免疫反应。BAPs 引发广谱 T 细胞反应，最终有效根除 71.4%的已建立肿瘤。值得注意的是，BAPs 疫苗接种引发持久的 T 细胞反应，提供强大的保护，100%的小鼠免受肿瘤再挑战的影响，肿瘤发病率显著降低 87.5%。此外，BAPs 与检查点阻断疗法协同抑制免疫原性较差的乳腺癌模型中的肿瘤生长。仿生方法为个性化癌症免疫治疗提供了一种具有高通用性的强大纳米疫苗配方。
