Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes

Magnetoliposomes (MLs) conjugated with an antibody fragment to give specifi city to a tumor were applied to hyperthermia for cancer. The Fab' fragment of the G250 antibody, which binds to MN antigen on many types of human rena l cell carcinoma, was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The targetabili ty of the G250-Fab' fragment-conjugating MLs (G250-FMLs) was investigated u sing the mouse renal cell carcinoma (mRCC) and MN antigen-presenting cell, MN-mRCC. The amount of G250-FMLs uptake reached 67 pg/cell against MN-mRCC cells in an in vitro experiment using plastic dishes and this value was abo ut 6 times higher than that in the case of MLs. In an in vivo experiment us ing MN-mRCC-harboring mice, 1.5 mg of the FMLs per carcinoma tissue accumul ated (tumor weight was 0.19 g), which corresponded to approximately 50% of the total injection. This value was 27 times higher than that of the MLs. A fter injection of the FMLs, mice were exposed to intracellular hyperthermia using alternating magnetic field irradiation. The temperature of tumor tis sue increased to 43 degreesC and the growth of the carcinoma was strongly a rrested for at least 2 weeks. These results indicate the G250-FMLs could ta rget renal cell carcinoma cells in vitro and in vivo, and are efficiently a pplicable to the hyperthermic treatment of carcinoma.