title: A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth.
abstract: Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA(+) human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA(-) human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA(+) cancer cells. 1C8 has no direct influence on proliferation and migration of CEA(+) cells, however, NK cell-dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA(+) cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA(+) tumors.
authors.affiliation: *Clinical Biochemistry Unit Departments of †Immunoregulation and Immunodiagnostics ∥Surgical Oncology and Medical Oncology, Chittaranjan National Cancer Institute ‡Department of Molecular Medicine, Bose Institute, Kolkata, India §Pediatric Hematology Oncology, University of Iowa Children's Hospital, IA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Das
authors.forename: Subhasis
authors.initials: S
authors.lastname: Barik
authors.forename: Saptak
authors.initials: S
authors.lastname: Banerjee
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.forename: Koustav
authors.initials: K
authors.lastname: Sarkar
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
authors.forename: Smarajit
authors.initials: S
authors.lastname: Pal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D052179:Antigens, Plant / Q000276:immunology; D031601:Azadirachta / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002459:Cell Fusion; D003110:Colonic Neoplasms / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D006023:Glycoproteins / Q000276:immunology*; D006131:Growth Inhibitors / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000628:therapy; D018515:Plant Leaves / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D006131:Growth Inhibitors; D010940:Plant Proteins