We have developed a new method for specifically delivering liposomal model
drugs to tumor cells. Bispecific monoclonal antibodies (bsMAb) (174H.64 x a
nti-biotin) which can bind tumor-specific antigen and biotin were developed
and characterized. Biotinylated stealth liposome loaded with model drug Tc
-99m-DTPA can bind to the biotin-binding arm of bsMAb. This targeted liposo
mal delivery strategy was tested in mouse KLN-205 squamous carcinoma model,
bsMAbs were administered 24 h in advance into tumor allograft bearing mice
, which allow them to bind to tumor cells through the anti-tumor binding ar
m. After clearance of circulating bsMAb, biotinylated stealth liposomes wer
e 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/liposom
e strategy show the broad possibilities of selective delivery of cytotoxic
drugs or genes to the specific targets.