title: Evaluation of ricin A chain-containing immunotoxins directed against glycolipid and glycoprotein on mouse lymphoma cells.
abstract: Immunotoxins composed of monoclonal antibodies (mAbs) and various toxins have been developed for the treatment of malignancies. We investigated the efficacy of three ricin toxin A-chain (RTA)-containing immunotoxins (ITs) conjugated from mAbs which recognize glycolipid asialo-GM2 and glycoprotein H-2d. These ITs retained the same immunoreactivity with mAbs. We evaluated the cytotoxicity of these ITs against mouse lymphoma cells L5178Y variants showing high (AA12,CC9) and low (27AV) expression of asialo-GM2. Anti-H-2d-RTA IT had the strongest cytotoxicity for all cell lines. Anti-asialo-GM2 (IgM)-RTA IT had stronger cytotoxicity than anti-asialo-GM2 (IgG3)-RTA IT. Anti-asialo-GM2-RTA ITs had different cytotoxicity against AA12 and CC9 cells. The establishment of appropriate anti-glycolipid mAbs may lead to effective immunotargeting therapy.
authors.affiliation: First Department of Internal Medicine, Okayama University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Usui
authors.forename: S
authors.initials: S
authors.lastname: Hakomori
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D014408:Biomarkers, Tumor / Q000032:analysis; D005069:Evaluation Studies as Topic; D005732:Gangliosides; D006023:Glycoproteins / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis*; D000922:Immunotoxins / Q000737:chemistry*; D008223:Lymphoma / Q000628:therapy*; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis*; D012276:Ricin / Q000032:analysis*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides; D006023:Glycoproteins; D006028:Glycosphingolipids; D000922:Immunotoxins; D009363:Neoplasm Proteins; C038244:ganglio-N-triaosylceramide; D012276:Ricin