Evaluation of ricin A chain-containing immunotoxins directed against glycolipid and glycoprotein on mouse lymphoma cells.
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.
Usui
H
H
First Department of Internal Medicine, Okayama University Medical School, Japan.
Hakomori
S
S
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
D014408:Biomarkers, Tumor; D005732:Gangliosides; D006023:Glycoproteins; D006028:Glycosphingolipids; D000922:Immunotoxins; D009363:Neoplasm Proteins; C038244:ganglio-N-triaosylceramide; D012276:Ricin