Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Sci Bull (Beijing). 2024 Aug 30;69(16):2565-2579. doi: 10.1016/j.scib.2024.06.016. Epub 2024 Jun 14.
Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine's effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer.
具核梭杆菌（Fusobacterium nucleatum，F. nucleatum）是一种口腔厌氧菌，普遍存在于结直肠癌中，与癌细胞生长、转移增加和治疗效果差密切相关。能够选择性消除细菌的细菌疫苗为靶向肿瘤内 F. nucleatum 提供了一种很有前途的方法，从而增强癌症治疗效果。尽管已经使用了佐剂来增强免疫反应，但由于需要足够的 T 细胞激活来清除细胞内病原体，疫苗的效果受到限制。在这项研究中，我们通过将高度免疫刺激性佐剂胆固醇修饰的 CpG 寡核苷酸整合到源自自体的 F. nucleatum 膜中，开发了一种极简仿生纳米疫苗。与由灭活细菌和 Alum 佐剂组成的传统疫苗相比，纳米疫苗与细菌膜和佐剂结合后，能够显著改善多种抗原和佐剂共递送至树突状细胞的效果，最大限度地提高其有效抗原呈递和下游免疫进展的能力。值得注意的是，该纳米疫苗具有出色的预防性和治疗性效果，可在不影响肿瘤内和肠道微生物群的情况下消除 F. nucleatum。它显著提高了化疗的疗效，并减少了具核梭杆菌感染的结直肠癌的转移。总体而言，这项工作代表了细菌纳米疫苗的合理应用，并为增强针对细菌感染癌症的抗肿瘤效果提供了蓝图。
