Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy

Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune dis...

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Main Authors: Shixue Chen, Lingling Li, Fan Zhang, Yu Wang, Yi Hu, Lei Zhao
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/4516041
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author Shixue Chen
Lingling Li
Fan Zhang
Yu Wang
Yi Hu
Lei Zhao
author_facet Shixue Chen
Lingling Li
Fan Zhang
Yu Wang
Yi Hu
Lei Zhao
author_sort Shixue Chen
collection DOAJ
description Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs. Multiple recombinant strategies have been used to solve the mispairing problem between light and heavy chains, as well as to enforce accurate dimerization of heterologous heavy chains. There are 23 platforms available to generate 62 BsAbs which can be further divided into IgG-like ones and fragment-based ones, and more than 50 molecules are undergoing clinical trials currently. BsAbs with IgG-like architecture exhibit superior advantages in structure (similar to natural antibodies), pharmacokinetics, half-life, FcR-mediated function, and biological activity. This review considers various IgG-like BsAb generation approaches, summarizes the clinical applications of promising new BsAbs, and describes the mechanism of BsAbs in tumor therapy.
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publishDate 2019-01-01
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series Journal of Immunology Research
spelling doaj-art-1b42c271283b4c44b1cf5a735ea90eba2025-02-03T01:09:44ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/45160414516041Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor TherapyShixue Chen0Lingling Li1Fan Zhang2Yu Wang3Yi Hu4Lei Zhao5National Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaNational Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaNational Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaNational Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaNational Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaNational Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, ChinaBispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs. Multiple recombinant strategies have been used to solve the mispairing problem between light and heavy chains, as well as to enforce accurate dimerization of heterologous heavy chains. There are 23 platforms available to generate 62 BsAbs which can be further divided into IgG-like ones and fragment-based ones, and more than 50 molecules are undergoing clinical trials currently. BsAbs with IgG-like architecture exhibit superior advantages in structure (similar to natural antibodies), pharmacokinetics, half-life, FcR-mediated function, and biological activity. This review considers various IgG-like BsAb generation approaches, summarizes the clinical applications of promising new BsAbs, and describes the mechanism of BsAbs in tumor therapy.http://dx.doi.org/10.1155/2019/4516041
spellingShingle Shixue Chen
Lingling Li
Fan Zhang
Yu Wang
Yi Hu
Lei Zhao
Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
Journal of Immunology Research
title Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
title_full Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
title_fullStr Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
title_full_unstemmed Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
title_short Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy
title_sort immunoglobulin gamma like therapeutic bispecific antibody formats for tumor therapy
url http://dx.doi.org/10.1155/2019/4516041
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AT fanzhang immunoglobulingammaliketherapeuticbispecificantibodyformatsfortumortherapy
AT yuwang immunoglobulingammaliketherapeuticbispecificantibodyformatsfortumortherapy
AT yihu immunoglobulingammaliketherapeuticbispecificantibodyformatsfortumortherapy
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