Clinical Significance of Liposome-Encapsulated OK-432 Injection with Simultaneous Interventional Radiological Treatment of Hepatocellular Carcinoma Based on Experimental Analysis of Liver-Associated Lymphocytes

OK-432 is a biological response modifier used in Japan to augment host immunity and is known to increase the host antitumor response. Using liposomes, which are vesicles made of phospholipids that have a structure resembling the cell membrane, we encapsulated OK-432. Encapsulated OK-432 was injected into the tail veins of mice, and its effect was compared with that of unencapsulated OK-432 given intravenously. In mice receiving either form of OK-432, both natural killer (NK) and intermediate TCR cells (intrahepatic T cells generated by extrathymic differentiation) increased markedly in the liver, with the peak level occurring 3 days after administration. Both forms of OK-432 also increased cytotoxic activity against Yac-1 cells. The increase of cells and cytotoxic activity in the liver persisted for longer in mice receiving encapsulated OK-432 than in animals receiving unencapsulated OK-432. Because both NK and intermediate TCR cells play an important role in tumor immunity, it may be useful for the treatment of tumors, particularly hepatocellular carcinoma. Local recurrence rate of hepatocellular carcinoma treated with liposome-encapsulated OK- 432 and simultaneous segmental lipiodol transcatheter arterial embolization (TAE) therapy was significantly lower than without OK-432 (P > .02).