CD4 and CD7 molecules as targets for drug delivery from antibody bearing liposomes.
We have examined two T lymphocyte cell surface molecules, CD4 and CD7, as targets for specific delivery of drugs from antibody-directed liposomes. The efficiency of uptake by peripheral lymphocytes, thymocytes, and two CEM sublines (CEM.MRS and CEM-T4) of anti-CD4 and anti-CD7 liposomes containing methotrexate was evaluated by the methotrexate-mediated inhibition of the incorporation of d-[3H]Urd into DNA. This was compared with similar liposomes targeted to MHC-encoded HLA class I molecules, which are known to be efficiently taken up by T cells. Despite the lower expression of CD7 molecules relative to HLA class I on most cell lines, CD7 was shown to be a good target for drug delivery. The results of an internalization study using radiolabeled Protein A showed that a higher proportion of CD7 molecules was internalized than HLA class I molecules. CD4-targeted liposomes, in contrast, were relatively ineffective for drug delivery for lymphoid cells, and only partially inhibited CEM-T4 cells. The lack of toxicity correlated with poor internalization of the target molecule on most cell lines. The drug effect of anti-CD4 liposomes was more pronounced on HeLa-T4, which is an epithelial cell line transfected with the CD4 gene. In contrast to lymphoid cells, these cells efficiently internalized CD4 molecules. PMA is known to down-regulate surface expression of CD4 molecules on various T cells. Internalization of CD4 was induced by PMA, but PMA failed to induce cytotoxicity of CD4-targeted liposomes for CEM.MRS. The internalized drug was probably degraded rapidly because internalized anti-CD4 antibody-bound Protein A was degraded very rapidly.
Suzuki
H
H
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Zelphati
O
O
Hildebrand
G
G
Leserman
L
L
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D004337:Drug Carriers; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008727:Methotrexate / Q000494:pharmacology; D013205:Staphylococcal Protein A / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D004337:Drug Carriers; D008081:Liposomes; D013205:Staphylococcal Protein A; D013755:Tetradecanoylphorbol Acetate; D008727:Methotrexate