Liposome-encapsulated OK-432 specifically and sustainedly induces hepatic natural killer cells and intermediate T cell receptor cells

Background: OK-432 is a biological response modifier used in Japan to augme nt host immunity and is known to increase the host antitumour response. By using liposomes, which are vesicles made from phospholipids that have a str ucture resembling the cell membrane, we encapsulated OK-432. Methods and Results: Encapsulated OK-432 was injected into the tail veins o f mice, and its effect was compared with that of unencapsulated OK-432 give n intravenously. In mice that received either form of OK-432, both the numb er of natural killer (NK) and intermediate T cell receptor (intTCR) cells ( intrahepatic T cells generated by extrathymic differentiation) increased ma rkedly in the liver, with the peak level occurring 3 days after administrat ion. Both forms of OK-432 also increased cytotoxic activity against Yac-1 c ells. The increase in numbers of cells and in cytotoxic activity in the liv er persisted for longer in mice that received encapsulated OK-432 than in a nimals that received unencapsulated OK-432. Conclusions: Because it has been shown that both NK and intTCR cells play a n important role in tumour immunity, an increase in the number of such cell s can be considered likely to have an increased antitumour effect. Encapsul ated OK-432 elicited liver-specific augmentation of cytotoxic activity and the effect was more persistent than that produced by OK-432 given in the co nventional form; therefore, it may be useful for the treatment of tumours, particularly those arising in the liver. (C) 2000 Blackwell Science Asia Pt y Ltd.