title: Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells.
abstract: Although current demands for therapeutic mAbs are growing quickly, production methods to date, including in vitro mammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here we describe the production of mAb BR55-2 (IgG2a) in transgenic plants that recognizes the nonprotein tumor-associated antigen Lewis Y oligosaccharide overexpressed in human carcinomas, particularly breast and colorectal cancers. Heavy and light chains of mAb BR55-2 were expressed separately and assembled in plant cells of low-alkaloid tobacco transgenic plants (Nicotiana tabacum cv. LAMD609). Expression levels of plant-derived mAb (mAbP) were high (30 mg/kg of fresh leaves) in T1 generation plants. Like the mammalian-derived mAbM, the plant mAbP bound specifically to both SK-BR3 breast cancer cells and SW948 colorectal cancer cells. The Fc domain of both mAbP and mAbM showed the similar binding to FcgammaRI receptor (CD64). Comparable levels of cytotoxicity against SK-BR3 cells were also shown for both mAbs in antibody-dependent cell-mediated cytotoxicity assay. Furthermore, plant-derived BR55-2 efficiently inhibited SW948 tumor growth xenografted in nude mice. Altogether, these findings suggest that mAbP originating from low-alkaloid tobacco exhibit biological activities suitable for efficient immunotherapy.
authors.affiliation: Biotechnology Foundation Laboratories, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Brodzik
authors.forename: Magdalena
authors.initials: M
authors.lastname: Glogowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bandurska
authors.forename: Monika
authors.initials: M
authors.lastname: Okulicz
authors.forename: Deepali
authors.initials: D
authors.lastname: Deka
authors.forename: Kisung
authors.initials: K
authors.lastname: Ko
authors.forename: Joke
authors.initials: J
authors.lastname: van der Linden
authors.forename: Jeanette H W
authors.initials: JH
authors.lastname: Leusen
authors.forename: Natalia
authors.initials: N
authors.lastname: Pogrebnyak
authors.forename: Maxim
authors.initials: M
authors.lastname: Golovkin
authors.forename: Zenon
authors.initials: Z
authors.lastname: Steplewski
authors.forename: Hilary
authors.initials: H
authors.lastname: Koprowski
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007167:Immunotherapy; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D046549:Plantibodies / Q000276:immunology*; D030821:Plants, Genetically Modified; D017452:Receptors, IgG / Q000276:immunology; D014026:Nicotiana / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D046549:Plantibodies; D017452:Receptors, IgG