Work

Engineering therapeutic antibodies targeting G-protein–coupled receptors

Year: 2016

Type: review

Abstract: G-protein–coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution. Antibody therapy that targets frequently occuring cellular receptors has become a possibility for the treatment of diverse diseases. Treatment with therapeutic antibodies has proven highly effective in several clinical settings. G-protein coupled receptors (GPCRs) are prime targets of such therapy, as there are over 800 different GPCRs, all crucial to cell signalling pathways. However, difficulty in isolating GPCRs from cells has prevented development of antibodies that target them. Migyeong Jo and San Taek Jung from Kookmin University, Korea, have reviewed new approaches to isolating GPCRs and synthesizing GPCR mimics that induce antibody production. Such advances have led to approval of one therapeutic antibody in Japan and to several clinical trials in the US and Europe. The authors predict that GPCR antibody therapy could be used to treat cancer, infection and inflammation in the near future.

Source: Experimental & Molecular Medicine

DOI: 10.1038/emm.2015.105

Authors: Migyeong Jo, Sang Taek Jung

Institution: Kookmin University

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,490