关键词: 肿瘤疫苗, 免疫治疗, 肿瘤微环境, 细菌载体, 病毒载体

Abstract:

The development of cancer vaccines is confronted with significant challenges. Synthetic biology emerges as a potent tool for addressing these challenges, due to its ability to modify and engineer microbes capable of adapting to and colonizing on tumor tissues to change the immunosuppressive tumor microenvironments, augment antigen presentations, and stimulate both innate and adaptive immune responses against tumors in situ. This review comments on several pivotal applications of synthetic biology in engineering bacterial and viral vectored cancer vaccines. We start with discussion on methods to mitigate the pathogenicity of bacterial or viral vectors, including the removal, deactivation, or modification of their virulent genes. Furthermore, we address strategies for enhancing their tropism and fitness within tumor tissues, such as the alteration of their cellular entry proteins or the implementation of environmentally controlled gene expression systems. Approaches to minimize their systemic toxicity are also described. To fully harness the potential of tumor microenvironment modifications induced by microbial replication, we underscore studies employing synthetic biology methods, which involve the introduction of foreign genes into the microbial genomes, thereby enabling the production of agents like cytokines, chemokines, or monoclonal antibodies to enhance the recruitment and activation of innate and adaptive cells, promote immunogenic cell death, and augment the presentation of tumor-associated antigens. We also delve into the applications of synthetic biology for the introduction of tumor antigens to the vectors, discussing various loading methods, locations, and releasing mechanisms to generate an optimized tumor-specific immune response. At the end, we highlight substantial challenges that arise in the development of microbial vectored cancer vaccines, including safety considerations, intricate interactions between anti-vector and anti-tumor immunity, and the inherent complexity of tumor biology, and propose strategies for addressing these obstacles. In conclusion, this review emphasizes the crucial role of synthetic biology in the engineering of microbes, which is instrumental in advancing the development of cancer vaccines. {L-End}

Key words: cancer vaccines, immunotherapy, tumor microenvironments, bacterial vectors, viral vectors