In vitro targeting and cytotoxicity of adriamycin in liposomes bearing monoclonal antibody against rat or human gp125 cell proliferation-associated antigen.
Chemoimmunoliposomes (CIL) were prepared by entrapping adriamycin in monoclonal antibody (mAb)-coated liposomes and examined for their binding capacity and cytotoxicity to relevant target tumor cells. Sonicated unilamellar liposomes were coated with B3 and HBJ127 mouse, mAbs, which recognize a rat and a homologous human cell proliferation-associated surface antigen, gp125, respectively, and then adriamycin was entrapped in the liposomes by means of transmembrane Na+/K+ gradients using valinomycin. These CIL selectively bound with relevant target tumor cells bearing the corresponding gp125 antigen, such as BC47 rat bladder cancer, FTL-13 rat thymic lymphoma, T24 human bladder cancer and Molt-4 human leukemia cells, although the binding capacities of the CIL to bladder cancer cells were relatively larger than those to lymphoma cells in both rat and human systems. This difference in the target cell binding was found to be attributable to the amount of gp125 antigen expressed on each target tumor cell, as determined by a Scatchard plot analysis. In accordance with the target cell binding capacities of CIL preparations, the CIL displayed much higher cytotoxic activity to bladder cancers than to lymphomas in both rat and human systems. In conjuction with our previous finding that gp125 antigen is expressed on tumor cells but not on resting normal cells, these findings indicate that CIL composed of anti-gp125 mAb will be useful for tumor therapy and that the antitumor efficacy is dependent upon the extent of the antigen expression on target tumor cells.
Tanaka
T
T
Department of Hygienic Chemistry, Tohoku University, Sendai.
Suzuki
S
S
Masuko
T
T
Hashimoto
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008081:Liposomes; D008223:Lymphoma / Q000276:immunology / Q000628:therapy; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology; D051381:Rats; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D000922:Immunotoxins; D008081:Liposomes; D009363:Neoplasm Proteins; D004317:Doxorubicin