Bispecific MAb aided liposomal drug delivery.
We have developed a new method for specifically delivering liposomal model drugs to tumor cells. Bispecific monoclonal antibodies (bsMAb) (174H.64 x anti-biotin) which can bind tumor-specific antigen and biotin were developed and characterized. Biotinylated stealth liposome loaded with model drug 99mTc-DTPA can bind to the biotin-binding arm of bsMAb. This targeted liposomal delivery strategy was tested in mouse KLN-205 squamous carcinoma model. bsMAbs were administered 24h in advance into tumor allograft bearing mice, which allow them to bind to tumor cells through the anti-tumor binding arm. After clearance of circulating bsMAb, biotinylated stealth liposomes were introduced to specifically bind to the tumor sites where bsMAb localized earlier. The results show that pretargeted bsMAb can enhance liposomal drug targeting by four times, 3.61% dose/g vs. 0.89% dose/g. This bsMAb/liposome strategy show the broad possibilities of selective delivery of cytotoxic drugs or genes to the specific targets.
Cao
Y
Y
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada. ying.cao@add.ssw.abbott.com
Suresh
M R
MR
D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001710:Biotin / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000276:immunology; D008081:Liposomes; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D015843:Serpins; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D004337:Drug Carriers; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008081:Liposomes; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D001710:Biotin; D016284:Technetium Tc 99m Pentetate