The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
School of Biopharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210023, China.
Adv Sci (Weinh). 2023 Oct;10(29):e2301835. doi: 10.1002/advs.202301835. Epub 2023 Aug 10.
Oncolytic bacteria are the most promising tumor target vector. Questions also remain regarding finding a balance between the therapeutic efficacy and safety of oncolytic bacteria. The critical measure of how this balance is maintained is the improvement in tumor colonization. Attenuated Salmonella typhimurium (VNP20009) as the only Salmonella strain to be evaluated in a clinical trial is a potential tumor therapeutic bacterium. A delivery system with controlled release of VNP after being loaded into neutrophils, which significantly increases the tumor-targeting of VNP and enhances its therapeutic efficacy in a melanoma lung metastasis model is constructed. To improve the synergistic therapeutic effect, a PD1 nanobody is applied to this system (NE(PD1nb)). NE(PD1nb) activate dendritic cells (DCs) differentiation and stimulate the M1-like differentiation of macrophages, and induce CD4 T-cells maturity and cytotoxic CD8 T-cells activation through DCs tumor antigen presentation.
溶瘤细菌是最有前途的肿瘤靶向载体。在寻找溶瘤细菌的治疗效果和安全性之间的平衡时，仍存在一些问题。维持这种平衡的关键措施是提高肿瘤定植率。减毒鼠伤寒沙门氏菌（VNP20009）是唯一一种在临床试验中进行评估的沙门氏菌菌株，是一种有潜力的肿瘤治疗细菌。构建了一种载有 VNP 的中性粒细胞控释递药系统，该系统可显著提高 VNP 的肿瘤靶向性，并增强其在黑素瘤肺转移模型中的治疗效果。为了提高协同治疗效果，将 PD1 纳米抗体应用于该系统（NE(PD1nb)）。NE(PD1nb)可激活树突状细胞（DCs）分化，并刺激巨噬细胞向 M1 样分化，通过 DCs 肿瘤抗原呈递诱导 CD4 T 细胞成熟和细胞毒性 CD8 T 细胞激活。
