Engineered bacteria: Strategies and applications in cancer immunotherapy
Shuhao Zhang, Rui Li, Yunxue Xu, Renfa Liu, Desheng Sun, Zhifei Dai
Abstract
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.