New methodology for liposome targeting to specific cells.

The specificity of liposomes for different cell types was achieved by conjugation to monoclonal antibodies directed against various cell surface antigens. L929 mouse fibroblast cells were targeted with liposomes conjugated to anti-H2Kk. K562 cells, a human line derived from chronic myelogenous leukemia, were targeted with antiglycophorin. One murine T-lymphoma, AKR/J SL2, was targeted with anti-thy 1.1; another, R1.1, was targeted with anti-H2Kk. The following important parameters were established concerning efficacy of antibody-directed liposomes as a drug delivery system. (1) Targeted liposomes containing methotrexate-gamma-aspartate were 20-40 times more cytotoxic than the free drug or nonspecific liposomes. (2) The use of drugs such as methotrexate-gamma-aspartate, which are unable to enter cells without a carrier, eliminates the nonspecific effects of drug that may leak from the liposomes. (3) Liposomes conjugated to antibody have a higher valency than the soluble antibody and bind to cells with up to 1000-fold higher affinity constant. (4) Liposomes that interact with more than one type of ligand on the cell surface show marked resistance to inhibition of cell association by soluble ligands. (5) The optimal liposome size appears to vary from 0.05 to 0.1 mu, depending on target cell type.