title: Human lymphocyte and monocyte lysis of tumor cells mediated by a mouse/human IgG1 chimeric monoclonal antibody.
abstract: The mouse monoclonal antibody 17-1A (gamma 2a, kappa) recognizes a tumor-associated antigen expressed on human gastrointestinal malignancies and has been used in Phase I and II clinical trials. Chimeric genetic constructs have been produced using 17-1A variable region genes (VL and VH) and the constant region genes for human kappa light chains and gamma 1 heavy chains (C kappa and gamma 1). The chimeric gene constructs were transfected into mouse myeloma cells for antibody production. The secreted mouse/human chimeric antibody contains the antigen-binding domain of 17-1A and the human (gamma 1, kappa) constant regions. Native mouse 17-1A and the chimeric antibody (chIgG1) were analyzed for binding to two human colon cancer cell lines and for the mediation of cancer cell line antibody-dependent cellular cytotoxicity by normal human peripheral blood lymphocytes and monocytes in 4 h 51Cr-release assays. The 17-1A and chIgG1 gave similar results in these in vitro biologic assays. This study demonstrates the feasibility of using mouse/human chimeric antibodies in human therapeutic applications.
authors: Comprehensive Cancer Center, University of Alabama, Birmingham 35294.
authors: D R
authors: DR
authors: Shaw
authors: G
authors: G
authors: Harrison
authors: L K
authors: LK
authors: Sun
authors: C
authors: C
authors: Shearman
authors: J
authors: J
authors: Ghrayeb
authors: S
authors: S
authors: McKinney
authors: P E
authors: PE
authors: Daddona
authors: A F
authors: AF
authors: LoBuglio
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins