Targeting of tumor-associated antigens (TAA) in experimental immunotherapy.
We have previously shown the superiority of tumor-associated antigens (TAA) to function as effective immunogens when administered with bilayer membrane vesicles called liposomes. The ability of liposomes to target TAA to host antigen-presenting cells is analyzed here. 1-Butanol extracted TAA from two syngeneic rat colon cancer tumors (WB 2054 and W 1756) was radioiodinated (131I-TAA). Free 131I and 131I-TAA (2.8 X 10(7) cpm and 75 micrograms TAA per rat) were used as tracers, with or without incorporation into liposomes (composition: sphingomyelin, cholesterol, dicetyl phosphate at 70:24:6 molar ratio). Six groups of male rats (BN X WF for WB2054 and Wistar/Furth for W1756, n = 18 each group) were injected iv with either free tracers or the tracers incorporated into liposomes. Whole blood clearance curve was biphasic (half-life alpha = 5 min; half life beta = 12 hr), suggesting a two-compartmental model of distribution. Seven animals from each group were sacrificed at set times (15 min to 48 hr), organs harvested and cpm/g of tissue estimated. Liposome 131I and liposome 131I-TAA were targeted to and retained preferentially in liver and spleen. Four animals from each group were imaged serially using a gamma camera. Matched pair analysis of regions showed persistently higher activity in liver-spleen area when liposomes were used (P less than 0.001). The uptake of radiolabeled antigens by plastic adherent mononuclear cells in liver and spleen was significantly higher when presented with liposomes (macrophage uptake index: liver = 1.65 vs 0.55; spleen = 5.85 vs 1.15; with and without liposomes, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D007167:Immunotherapy; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011877:Radionuclide Imaging; D051381:Rats; D011914:Rats, Inbred BN; D011920:Rats, Inbred WF; D013154:Spleen / Q000276:immunology
D000951:Antigens, Neoplasm; D008081:Liposomes