Hepatic immunopotentiation by galactose-entrapped liposomal IL-2 compound in the treatment of liver metastases.
To activate hepatic sinusoidal lymphocytes (HSL) and increase the local antitumor activity in the liver, we developed a liver-targeted interleukin-2 (IL-2) compound using a galactose residue-entrapped liposome. We prepared various kinds of IL-2-containing liposomes made by the hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 followed by the combination with galactose residues to facilitate the selective uptake by liver parenchymal cells bearing galactose receptors. The IL-2 liposomes were given to C3H/He mice followed by the determination of: (1) organ distribution by 125I-labeled IL-2, (2) antitumor activity of hepatic sinusoidal lymphocytes by 51Cr-release assay, and (3) in vivo antitumor efficacy by the measurement of hepatic metastases. When galactose-entrapped IL-2 liposomes (Gallip-IL-2) were administered, a significantly greater hepatic accumulation of IL-2 was seen for up to 2 weeks compared to IL-2 liposomes or free IL-2. According to these results, the antitumor activity of HSL was significantly augmented. Moreover, when mice with hepatic micrometastases were treated with Gal-lip-IL-2, the area of hepatic metastases was significantly reduced. These findings thus indicate that Gal-lip-IL-2 may enhance the therapeutic efficacy of IL-2 against hepatic metastases and thereby facilitate a more practical daily dosing regimen.
Okuno
K
K
First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.
Nakamura
K
K
Tanaka
A
A
Yachi
K
K
Yasutomi
M
M
D000818:Animals; D004337:Drug Carriers; D005690:Galactose; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008081:Liposomes; D008099:Liver / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D005690:Galactose