Role of ligand in antibody-directed endocytosis of liposomes by human T-leukemia cells.
The rate of uptake and intracellular processing of ligand-directed drug carriers may depend heavily on the endocytic pathway of the target antigen. We examined the role of the target antigen and type of antibody-liposome linkage in determining endocytosis of liposomes by three human T-cell leukemias, Jurkat, CEM, and Molt-4. Liposome-cell binding and internalization over time were studied using two independent assays for intracellular delivery of liposome contents: a new fluorescence assay using a pH-sensitive fluorescent dye; and a growth inhibition assay for delivery of cytotoxic drug, methotrexate-gamma-aspartate. Liposomes targeted against the transferrin receptor showed greater surface binding, internalization, and growth inhibition than liposomes targeted against the T-cell surface antigens, CD2, CD3, or CD5. Furthermore, liposomes made by conjugating the targeting antibody directly to the liposome surface were more efficiently internalized and retained than were liposomes linked to antibody-coated cells via Protein A. Selection of the type of antibody-liposome conjugate as well as the appropriate surface receptor to facilitate endocytosis is essential in antibody-directed drug treatment of cancer.
Matthay
K K
KK
Department of Pediatrics, University of California, San Francisco 94143.
Abai
A M
AM
Cobb
S
S
Hong
K
K
Papahadjopoulos
D
D
Straubinger
R M
RM
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D004705:Endocytosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D008024:Ligands; D008081:Liposomes / Q000276:immunology / Q000493:pharmacokinetics*; D008856:Microscopy, Fluorescence; D011990:Receptors, Transferrin / Q000276:immunology; D013205:Staphylococcal Protein A / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D011990:Receptors, Transferrin; D013205:Staphylococcal Protein A