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中国生物工程杂志

China Biotechnology
China Biotechnology  2022, Vol. 42 Issue (10): 39-50    DOI: 10.13523/j.cb.2204001
    
Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy
Chun-li HAN,Han-jie WANG*()
School of Life Sciences, Tianjin University, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecules,Tianjin 300072, China
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Abstract  

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.



Key wordsLive biotherapeutics      Synthetic biology      Tumor immunotherapy     
Received: 01 April 2022      Published: 04 November 2022
ZTFLH:  Q819  
Corresponding Authors: Han-jie WANG     E-mail: wanghj@tju.edu.cn
Cite this article:

Chun-li HAN,Han-jie WANG. Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy. China Biotechnology, 2022, 42(10): 39-50.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2204001     OR     https://manu60.magtech.com.cn/biotech/Y2022/V42/I10/39

Fig.1 The receptor design of engineered live human cell biotherapeutics
商品名 抗原靶点 适用证 公司 批准年份
KYMRIAH CD19 复发或难治性急性淋巴细胞白血病 Novartis 2017
YESCARTA CD19 复发或难治性B细胞淋巴瘤 Kite Pharma Inc. 2018
TECARTUS CD19 复发或难治性套细胞淋巴瘤 Kite Pharma Inc. 2020
ABECMA BCMA 复发或难治性多发性骨髓瘤 BMS 2021
BREYANZI CD19 复发或难治性B细胞淋巴瘤 BMS 2021
瑞基奥仑赛注射液 CD19 复发或难治性B细胞淋巴瘤 药明巨诺 2021
CARVYKTI BCMA 复发或难治性多发性骨髓瘤 传奇生物 2022
Table 1 Approved engineered live CAR-T cell biotherapeutics
Fig.2 Three steps in the functioning of oncolytic virus biotherapeutics
商品名 适用证 公司 批准机构 批准年份
Rigvir 黑色素瘤 Latima 拉脱维亚药品管理署 2004
安柯瑞 晚期鼻咽癌 上海三维 中国国家食品药品监督管理总局 2005
Imlygic(T-Vec) 黑色素瘤 Kite Pharma Inc. 美国食品药品监督管理局 2015
Delytact 恶性胶质瘤 传奇生物 日本厚生劳动省 2021
Table 2 Approved oncolytic virus biotherapeutics
Fig.3 The genetic circuit design of engineered live bacterial biotherapeutics
底盘类型 商品名 适用证 公司 临床试验段
大肠杆菌 SYNB1891 转移性实体瘤、淋巴瘤 Synlogic I期
VAX014 膀胱移行细胞癌 Vaxiion I期
沙门氏菌 VNP20009 实体瘤、转移瘤 Vion Pharma. I期
VXM01 复发性胶质母细胞瘤 Vaximm GmbH I/II期
双歧杆菌 APS001F 实体瘤 Anaeropharma Science I/II期
EDP1503 复发性结直肠癌 Evelo Biosciences I/II期
李斯特菌 ADXS31-142 前列腺癌 Advaxis I/II期
CRS-207 胰腺癌 约翰霍普金斯大学 II期
Table 3 Clinical trials of engineered live bacterial biotherapeutics for tumor immunotherapy
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