工程生物活药在肿瘤免疫治疗中的应用

人体细胞、细菌、病毒等生命体可以改造为工程生物活药,可在患者体内维持生物活性、自我复制并表达基因。相比于传统药物,工程生物活药在体内维持疗效时间长,具备外源基因表达能力,可实现多功能性和稳态调控,且具有独特的靶向、响应等能力。近年来,工程生物活药在肿瘤免疫治疗中的应用受到广泛关注,CAR-T等细胞治疗、溶瘤病毒疗法已在临床中获得良好的疗效,工程菌也在临床和临床前研究中发展迅猛。细胞、细菌、病毒三类活药的特性和治疗机制不同,因此具有不同的设计目的与思路。随着合成生物学技术的发展,工程生物活药将更安全、更高效,也将为肿瘤治疗带来新的机遇。针对工程生物活药在肿瘤免疫治疗中应用的最新进展开展了综述,阐述了不同生物活药的合成生物学设计和免疫治疗机制。

Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy

Living organisms such as cells isolated from human body, bacteria, and viruses can be engineered as live biotherapeutics, which can maintain biological activity, self-replicate, and express genes in a patient’s body. Compared with traditional drugs, engineered live biotherapeutics maintain a relatively long-time curative effect in vivo, express genes as expected to achieve versatility and homeostasis control, and have unique targeting and response capabilities. In recent years, the application of engineered live biotherapeutics in tumor immunotherapy has received widespread attention. CAR-T and other cell therapies and oncolytic virus therapies have performed good clinical effects, and engineered bacteria are also developing rapidly in clinical and preclinical research. Among all the types of engineered live biotherapeutics, human cells, bacteria, and viruses have different characteristics. Therefore, their design purposes and ideas are different. With the progress of synthetic biology technologies, engineered live biotherapeutics will have better safety and efficacy, and bring new opportunities for tumor therapy. Herein, the latest developments of engineered live biotherapeutics for tumor immunotherapy are reviewed, and the synthetic biology design and immunotherapy mechanisms are expounded.