Anti-CD22 Onconase: preparation and characterization.
Antibodies can be conjugated to effector molecules to derive targeted therapeutics with properties such as cell-specific cytotoxicity. The murine anti-CD22 antibody RFB4 linked to a member of the ribonuclease A superfamily, Onconase (Onc), becomes a potential drug candidate for non-Hodgkin's lymphoma. Onc is currently in Phase III clinical trials for unresectable malignant mesothelioma but conjugation to RFB4 considerably enhances its specificity for CD22+ lymphomas. RFB4-targeted Onc is effective in preclinical models, causes little non-specific toxicities in mice, and has favorable formulation properties. Derivatization and conjugation of RFB4 and Onc have been optimized.
Newton
Dianne L
DL
NCI-Frederick, National Institutes of Health, Frederick, MD, USA.
Stockwin
Luke H
LH
Rybak
Susanna M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004220:Disulfides / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D012343:RNA, Transfer / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012260:Ribonucleases / Q000096:biosynthesis* / Q000276:immunology* / Q000302:isolation & purification; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D013388:Succinimides
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004220:Disulfides; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D013388:Succinimides; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D012343:RNA, Transfer; D012260:Ribonucleases; C058703:ranpirnase