Tumor cell lysis and tumor growth inhibition by the isotype variants of MAb BR55-2 directed against Y oligosaccharide.
IgG3 murine MAb BR55-2 is directed against adenocarcinoma associated Y oligosaccharide. Isotype IgG1, IgG2b and IgG2a switch variants of the BR55-2 antibody were compared in antibody dependent-cell mediated cytotoxicity (ADCC) and complement mediated cytotoxicity (CDC) assays in the murine system. IgG3, IgG2a and IgG2b isotypes mediated ADCC with murine macrophages. Murine splenocytes mediated low levels of ADCC, with IgG3 and IgG2a being always more effective than IgG1 and IgG2b isotypes. All four isotypes were ineffective in CDC with murine serum as a source of complement. In the in vivo experiments, growth of human tumors xenotransplanted into nude mice was best inhibited by both IgG3 and IgG2a isotypes while IgG1 protein was the least effective. Thus, IgG3 and IgG2a isotypes are the most efficient proteins for cancer immunotherapy since they mediate the highest tumoricidal activities in vitro and in vivo.
Steplewski
Z
Z
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Lubeck
M D
MD
Scholz
D
D
Loibner
H
H
McDonald Smith
J
J
Koprowski
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D001943:Breast Neoplasms; D002455:Cell Division; D003110:Colonic Neoplasms; D003602:Cytotoxicity, Immunologic; D005260:Female; D006028:Glycosphingolipids / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D013274:Stomach Neoplasms
D000911:Antibodies, Monoclonal; D006028:Glycosphingolipids; D007074:Immunoglobulin G; C055089:Y glycolipid