Zhang Shuhao, Li Rui, Xu Yunxue, Liu Renfa, Sun Desheng, Dai Zhifei
Department of Biomedical Engineering, College of Future Technology, National Biomedical Imaging Center, Peking University, Beijing 100871, China.
Department of Ultrasonic Imaging, Peking University Shenzhen Hospital, Shenzhen 518035, China.
Fundam Res. 2024 Nov 13;5(3):1327-1345. doi: 10.1016/j.fmre.2024.11.001. eCollection 2025 May.
Cancer therapy remains a critical medical challenge. Immunotherapy is an emerging approach to regulating the immune system to fight cancer and has shown therapeutic potential. Due to their immunogenicity, bacteria have been developed as drug-delivery vehicles in cancer immunotherapy. However, ensuring the safety and efficacy of this approach poses a considerable challenge. This paper comprehensively explains the fundamental processes and synthesis principles involved in immunotherapy utilizing engineered bacteria. Initially, we list common engineered strains and discuss that growth control through genetic mutation promises therapeutic safety. By considering the characteristics of the tumor microenvironment and the interaction of specific molecules, the precision targeting of tumors can be improved. Furthermore, we present a foundational paradigm for genetic circuit construction to achieve controlled gene activation and logical expression, directly determining drug synthesis and release. Finally, we review the immunogenicity, the expression of immunomodulatory factors, the delivery of immune checkpoint inhibitors, and the utilization of bacteria as tumor vaccines to stimulate the immune system and facilitate the efficacy of cancer immunotherapy.
癌症治疗仍然是一项严峻的医学挑战。免疫疗法是一种新兴的调节免疫系统以对抗癌症的方法，已显示出治疗潜力。由于细菌具有免疫原性，它们已被开发为癌症免疫疗法中的药物递送载体。然而，确保这种方法的安全性和有效性带来了相当大的挑战。本文全面解释了利用工程菌进行免疫疗法所涉及的基本过程和合成原理。首先，我们列出常见的工程菌株，并讨论通过基因突变进行生长控制有望实现治疗安全性。通过考虑肿瘤微环境的特征和特定分子的相互作用，可以提高肿瘤的精准靶向性。此外，我们提出了一种基因回路构建的基本范式，以实现可控的基因激活和逻辑表达，直接决定药物的合成和释放。最后，我们综述了免疫原性、免疫调节因子的表达、免疫检查点抑制剂的递送以及利用细菌作为肿瘤疫苗来刺激免疫系统并促进癌症免疫疗法的疗效。
