Targeted delivery of diphtheria toxin via immunoliposomes: efficient antitumor activity in the presence of inactivating anti-diphtheria toxin antibodies.
Diphtheria toxin (DT) has attracted considerable attention for anti-cancer therapy. However, its extensive use is prohibited by (i) its non-specific action which can result in substantial toxicity, (ii) most patients have low serum levels of anti-DT antibodies (AT antibodies) which can inactivate DT and (iii) its immunogenicity will boost the circulating AT antibody level, thereby further compromising the antitumor activity. To overcome these limitations, we have developed a new approach for targeted delivery of DT utilizing immunoliposomes. In this approach, protection against the non-specific action of DT is combined with efficient antitumor activity even in the presence of inactivating AT antibodies.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
M H
MH
Vingerhoeds
P A
PA
Steerenberg
J J
JJ
Hendriks
D J
DJ
Crommelin
G
G
Storm
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D051379:Mice; D010051:Ovarian Neoplasms; D010713:Phosphatidylcholines
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol