title: Recognition based hormonal 95kDa monoclonal antibody on three human cancer cell lines for developing targeted radio-immuno-imaging and therapy.
abstract: The present study aimed to explore the possibility of developing a immuno-imaging/therapeutic agent for hCG-expressing tumors by using antibodies raised against them. Three human cancer cell lines were selected:lung adenocarcinoma (A549), glioblastoma (U87MG) and breast cancer (MCF7). Anti-β-hCG monoclonal antibody, obtained from ascitic fluid, was purified by affinity chromatography followed by characterization and titration. Ectopic expression of hCG on these cell lines was tested by flow cytometry and in-vitro cytotoxicity with antibodies was tested by MTT assay on the cell line with the highest percentage binding. For positive and negative controls, immortalized trophoblast cells (SW71) and peripheral blood monocytes were used. Antibody was then radiolabeled with lutetium-177 ((177)Lu) and in vivo biodistribution studies were conducted in murine tumor model. Antibodies could be purified to homogeneity with a concentration 28mg/mL. Percentage receptor expression on A549, U87MG and MCF7 cells was 95%, 66% and 55% respectively. About 90% of A549 cells could be killed with antibody at 72h post-treatment. No cytotoxicity was observed on SW71 despite a high binding percentage (96%). Antibodies were radiolabeled with high efficiency (∼98%). In-vivo studies using radiolabeled antibodies showed hepato-biliary excretion route and significant uptake in A549 tumor. In conclusion, among the 3 cancer cell lines, lung adenocarcinoma significantly expresses β-hCG and shows dose dependent cytotoxicity with anti-β-hCG antibody. Radiolabeling of this antibody can aid in imaging and also has the potential of enhancing its therapeutic potential. This study provides a platform for further studies for targeted radio-immuno imaging and subsequent therapy of hCG-expressing cancers.
authors: Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India. guru47@gmail.com
authors: Guru Pad
authors: GP
authors: Bandopadhyaya
authors: Geetanjali
authors: G
authors: Arora
authors: Jaya
authors: J
authors: Shukla
authors: Sourabh
authors: S
authors: Ghosh
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D008970:Molecular Weight; D016719:Radioimmunodetection / Q000379:methods*; D016499:Radioimmunotherapy / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D018997:Chorionic Gonadotropin, beta Subunit, Human