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Engineering >> 2021, Volume 7, Issue 11 doi: 10.1016/j.eng.2020.06.030

Modified Therapeutic Antibodies: Improving Efficacy

a Department of Cell Biology, National Translational Science Center for Molecular Medicine, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an 710032, China
b Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
c Department of Hepatobiliary Surgery, Air Force Medical Center, Beijing 100142, China

Received: 2019-09-29 Revised: 2020-04-14 Accepted: 2020-06-24 Available online: 2021-07-28

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Abstract

The prosperity of the biotherapeutics market reflects the feasibility and effectiveness of therapeutic antibodies for the treatment of cancers, inflammatory disorders, and refractory infections. As drawbacks emerge in clinical trials and practice, such as impeded binding, reduced effector functions, and frequent adverse reactions, modifications of therapeutic antibodies are unprecedently burgeoning in research and development (R&D). These modifications include: ① modified glycosylation; ② fragment of crystallizable domain (Fc) amino acid alterations; ③ cross-isotype or cross-subclass exchanges; ④ antibody–drug conjugates (ADCs); ⑤ single chain of variable region fragment (scFv) for chimeric antigen receptor T (CAR-T) cells; and ⑥ bispecific antibodies (bsAbs) in order to promote binding affinity, half-life in circulation, effectiveness toward target cells and, ultimately, to achieve overall improved efficacy. While many achievements have been made around the world in the past decades, China has been playing an active role in this realm, with its great demand for biotherapeutics with R&D potential. This review recapitulates the international progress that has been achieved with modified therapeutic antibodies, and then focuses on that of China in an independent section.

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