title: Camel heavy chain antibodies against prostate-specific membrane antigen.
abstract: Prostate-specific membrane antigen (PSMA), a type II integral membrane glycoprotein, is highly overexpressed in all forms of prostate cancer tissues. It has also been demonstrated in a wide range of neovasculature of non-prostatic solid tumors, including bladder, pancreas, lung, kidney, colorectal, and gastric cancers. Given the unique expression of PSMA, it is considered an alluring target for antibody-based imaging and therapy of cancer. In the present study, the production and characterization of camel heavy chain antibodies (HCAbs) specific for the external domain of the PSMA are reported. Due to the absence of the CH1 domain, HCAbs are smaller than their counterparts in conventional antibodies. In this study, camel antibodies were generated through immunization of Camelus dromedarius with a synthetic 28 amino acid peptide corresponding to the external surface domain of antigen and PSMA-expressing cell lines. Different binding properties to protein A and protein G affinity columns were deployed to separate three subclasses of camel IgG. The affinity purified HCAbs bound selectively to the synthetic peptide in enzyme linked immunosorbent assay (ELISA) and reacted specifically with PSMA-expressing cell line through immunocytochemistry study. Currently, we are attempting to develop recombinant variable domain of these heavy chain antibodies (VHH or nanobody) for tumor imaging and cancer therapy.
authors.affiliation: Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Evazalipour
authors.forename: Bahram Soltani
authors.initials: BS
authors.lastname: Tehrani
authors.forename: Mohsen
authors.initials: M
authors.lastname: Abolhassani
authors.forename: Hamid
authors.initials: H
authors.lastname: Morovvati
authors.forename: Kobra
authors.initials: K
authors.lastname: Omidfar
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000302:isolation & purification; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D002162:Camelus; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D043425:Glutamate Carboxypeptidase II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011471:Prostatic Neoplasms; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D007143:Immunoglobulin Heavy Chains; D010446:Peptide Fragments; D012710:Serum Albumin, Bovine; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II