工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Progress in engineered bacterial cancer therapies.
Progress in engineered bacterial cancer therapies.
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工程化细菌正逐渐成为癌症疗法开发中的强大工具,这得益于合成生物学和肿瘤免疫学的进步。这些微生物优先定植于实体瘤,在那里它们可以将治疗剂直接递送至恶性细胞和肿瘤微环境中,诱导肿瘤细胞死亡并激活强大的抗肿瘤免疫应答。当前的策略包括编程细菌使其分泌毒素、肿瘤抑制蛋白或促凋亡蛋白,以及介导靶向的细胞内递送。细菌还可以被工程化改造以感知肿瘤特异性代谢物并黏附于肿瘤相关细胞表面抗原,进一步增强选择性和安全性。工程化菌株可与免疫疗法——包括免疫检查点抑制剂和CAR-T 细胞——产生协同作用,并且即使在远处转移部位也能刺激固有免疫和适应性免疫应答。在此,我们综述了该领域的最新进展,重点关注工程化策略及其在临床前体内肿瘤模型中的有效性,并概述了未来发展的前景和剩余挑战。
Engineered bacteria are emerging as powerful tools in the development of cancer therapies, driven by advances in synthetic biology and tumor immunology. These microbes preferentially colonize solid tumors, where they can deliver therapeutic agents directly to malignant cells and into the tumor microenvironment, inducing tumor cell death and activating robust anti-tumor immune responses. Current strategies include programming bacteria to secrete toxins, tumor-suppressor or pro-apoptotic proteins, and to mediate targeted intracellular delivery.
Bacteria can also be engineered to sense tumor-specific metabolites and to adhere to tumor-associated cell surface antigens, further enhancing selectivity and safety. Engineered strains synergize with immunotherapies - including immune checkpoint inhibitors and chimeric antigen receptor-T cells - and can stimulate both innate and adaptive immune responses, even at distant metastatic sites.
Here, we review recent progress in this field, with a focus on engineering strategies and their effectiveness in preclinical in vivo tumor models, and outline prospects for future developments and remaining challenges.
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