Enhanced antitumour effect of liposomal daunorubicin using antibody-phospholipase C conjugates or fusion protein.
We have developed a new two-step method for targeting cytotoxic drugs to tumour cells. The method firstly involves the binding to tumour cells of antibody-phospholipase C immunoconjugates or fusion proteins. Further to washing or clearance of the immunoconjugates, liposomes are introduced which are specifically lysed at the tumour site by PLC to release their cytotoxic contents in the vicinity of the tumour cells. For two alternative human cell lines, a synergistic inhibition of cell proliferation was seen for combined treatment with a specific immunoconjugate and daunorubicin encapsulated liposomes. For tumour xenografts in mice, the combined treatment resulted in an inhibition of tumour growth although with no eradication of tumours at the doses used. The two-step antibody-PLC/liposome approach offers broad possibilities for the precise delivery of payloads of cytotoxic drugs to tumour sites.
Carter
G
G
Biovation Limited, AURIS Business Centre, Aberdeen AB23 8XU, UK.
White
P
P
Fernie
M
M
King
S
S
McLean
G
G
Titball
R
R
Carr
F J
FJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage*; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D010738:Type C Phospholipases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D008081:Liposomes; D011993:Recombinant Fusion Proteins; C055966:immunoglobulin Fv; D066246:ErbB Receptors; D010738:Type C Phospholipases; D003630:Daunorubicin