Attenuated Bacteria‐Based Tumor Therapy: Clinical Application Risks, Marketing Approval Restrictions, and Coping Strategies

Bacteria-based cancer therapy is a promising cancer treatment strategy that utilizes genetically engineered attenuated bacteria to specifically target tumor tissues, directly kill cancer cells, or activate the host's immune response. Engineering modifications of attenuated bacteria can achieve more effective anti-tumor effects, and consequently, a number of clinical trials have been carried out. However, the clinical translation of attenuated bacteria faces multiple challenges, including safety risks, fluctuating therapeutic efficacy, difficulties in vivo monitoring, complex production quality control, and lack of regulatory approval standards. This review mainly summarizes five aspects of bacterial cancer therapy: the safety risks and attenuation strategies, the regulation of therapeutic stability, bacterial in vivo imaging technologies, the optimization of bacterial production processes, and market approval pathways. It aims to precisely control bacterial behavior through genetic circuits and enable real-time monitoring of the treatment process by means of multimodal imaging, ultimately promoting the clinical translation of attenuated bacterial therapy.