Membrane Proteins as Targets for Biological Drugs

Sood, Vanita D.; Gross, Alec W.

doi:10.1007/978-981-13-9077-7_3

Vanita D. Sood² &
Alec W. Gross²

744 Accesses
2 Citations

Abstract

Membrane proteins, as gateways to the cell, are good therapeutic targets for therapeutic antibodies and other biologics. Approved biologics employ a diverse array of mechanisms of action, both inhibitory or activating. Inhibitory mechanisms including competitive inhibition, antibody dependent cellular cytotoxicity, steric inhibition and receptor downregulation are described, exemplified by the biologics targeting various receptors of the EGFR family of type I single pass membrane proteins. The tendency of membrane proteins to internalize can be exploited to deliver toxic payloads to tumor cells using ADCs. Internalization of membrane proteins also influences the pharmacokinetics of biologics, due to target mediated drug disposition. In addition to TMDD, interactions with lipid membranes of cells or with the membrane protein FcRn also influence the PK of biologics. Finally, the targeting of the immunological synapse to activate anti-tumor immunity by biological drugs such as checkpoint inhibitors is described.

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Abbreviations

ADCC:: Antibody dependent cellular cytotoxicity
ADC:: Antibody drug conjugate
BVP:: Baculovirus particles
CAR:: Chimeric antigen receptor
CDC:: Complement dependent cytotoxicity
CRC:: Colorectal cancer
EGF:: Epidermal growth factor
EGFR:: Epidermal growth factor receptor
ELISA:: Enzyme linked immune-sorbent assay
HIC:: Hydrophobic interaction chromatography
INN:: International nonproprietary name
NSCLC:: Non small cell lung cancer
PD:: Pharmacodynamic
PK:: Pharmacokinetic
SPMP:: Single pass membrane protein
TMDD:: Target mediated drug disposition

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Vanita D. Sood & Alec W. Gross

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Department of Orthopaedics and Institute of Precision Medicine, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yu Cao

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Sood, V.D., Gross, A.W. (2019). Membrane Proteins as Targets for Biological Drugs. In: Cao, Y. (eds) Advances in Membrane Proteins. Springer, Singapore. https://doi.org/10.1007/978-981-13-9077-7_3

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