A Novel Human Antibody, HF, against HER2/erb-B2 Obtained by a Computer-Aided Antibody Design Method
Chunxia Qiao,
Ming Lv,
Xinying Li,
Xiaoling Lang,
Shouqin Lv,
Mian Long,
Yan Li,
Shusheng Geng,
Zhou Lin,
Beifen Shen,
Jiannan Feng
Affiliations
Chunxia Qiao
State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China; Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China
Ming Lv
Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Institute of Military Cognitive and Brain Sciences, Beijing 100850, China
Xinying Li
State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China; Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Institute of Military Cognitive and Brain Sciences, Beijing 100850, China
Xiaoling Lang
Beijing Mabworks Biotech Co. Ltd., Beijing 100176, China
Shouqin Lv
Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
Mian Long
Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
Yan Li
Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Institute of Military Cognitive and Brain Sciences, Beijing 100850, China
Shusheng Geng
Beijing Mabworks Biotech Co. Ltd., Beijing 100176, China
Zhou Lin
Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Institute of Military Cognitive and Brain Sciences, Beijing 100850, China
Beifen Shen
Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Institute of Military Cognitive and Brain Sciences, Beijing 100850, China; Corresponding authors.
Jiannan Feng
State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China; Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, China; Corresponding authors.
Fully human antibodies have minimal immunogenicity and safety profiles. At present, most potential antibody drugs in clinical trials are humanized or fully human. Human antibodies are mostly generated using the phage display method (in vitro) or by transgenic mice (in vivo); other methods include B lymphocyte immortalization, human–human hybridoma, and single-cell polymerase chain reaction. Here, we describe a structure-based computer-aided de novo design technology for human antibody generation. Based on the complex structure of human epidermal growth factor receptor 2 (HER2)/Herceptin, we first designed six short peptides targeting the potential epitope of HER2 recognized by Herceptin. Next, these peptides were set as complementarity determining regions in a suitable immunoglobulin frame, giving birth to a novel anti-HER2 antibody named “HF,” which possessed higher affinity and more effective anti-tumor activity than Herceptin. Our work offers a useful tool for the quick design and selection of novel human antibodies for basic mechanical research as well as for imaging and clinical applications in immune-related diseases, such as cancer and infectious diseases.