Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2017 Dec 2;493(4):1567-1572. doi: 10.1016/j.bbrc.2017.10.036. Epub 2017 Oct 7.

Whole-cell biopanning with a synthetic phage display library of nanobodies enabled the recovery of follicle-stimulating hormone receptor inhibitors.

Author information

1
Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), PSL Research University, Institut Curie, 26, Rue D'Ulm, Paris, France; CIC IGR Curie 1428, France.
2
Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), PSL Research University, Institut Curie, 26, Rue D'Ulm, Paris, France.
3
Translational Research Department, PSL Research University, Institut Curie, 26 Rue D'Ulm, F75248 Paris Cedex 05, France.
4
Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), PSL Research University, Institut Curie, 26, Rue D'Ulm, Paris, France; Translational Research Department, PSL Research University, Institut Curie, 26 Rue D'Ulm, F75248 Paris Cedex 05, France.
5
INSERM U932, PSL Research University, Institut Curie, 26 Rue D'Ulm, F75248 Paris, France; SIRIC INCa-DGOS-4654, France; CIC IGR Curie 1428, France.
6
UMR144, PSL Research University, Institut Curie, 12 Lhomond, 75005, Paris, France.
7
Tumor Target and Therapeutic Antibody - Identification Platform (TAb-IP), PSL Research University, Institut Curie, 26, Rue D'Ulm, Paris, France; SIRIC INCa-DGOS-4654, France; CIC IGR Curie 1428, France; Dept. of Biomedical Sciences and Engineering, University of Nova Gorica (UNG), Glavni Trg 9, SI-5261, Vipava, Slovenia. Electronic address: ario.demarco@ung.si.

Abstract

Antibodies are essential reagents that are increasingly used in diagnostics and therapy. Their specificity and capacity to recognize their native antigen are critical characteristics for their in vivo application. Follicle-stimulating hormone receptor is a GPCR protein regulating ovarian follicular maturation and spermatogenesis. Recently, its potentiality as a cancer biomarker has been demonstrated but no antibody suitable for in vivo tumor targeting and treatment has been characterized so far. In this paper we describe the first successful attempt to recover recombinant antibodies against the FSHR and that: i) are directly panned from a pre-immune library using whole cells expressing the target receptor at their surface; ii) show inhibitory activity towards the FSH-induced cAMP accumulation; iii) do not share the same epitope with the natural binder FSH; iv) can be produced inexpensively as mono- or bivalent functional molecules in the bacterial cytoplasm. We expect that the proposed biopanning strategy will be profitable to identify useful functional antibodies for further members of the GPCR class.

KEYWORDS:

Allosteric inhibitor; GPCR; Phage display; Recombinant antibody production; cAMP-dependent signaling

PMID:
29017919
DOI:
10.1016/j.bbrc.2017.10.036
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center