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

J Gastroenterol Hepatol. 2000 May;15(5):542-9. doi: 10.1046/j.1440-1746.2000.02188.x.

Abstract

Background: OK-432 is a biological response modifier used in Japan to augment host immunity and is known to increase the host antitumour response. By using liposomes, which are vesicles made from phospholipids that have a structure resembling the cell membrane, we encapsulated OK-432.

Methods and results: 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 that received either form of OK-432, both the number of natural killer (NK) and intermediate T cell receptor (intTCR) 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 in numbers of cells and in cytotoxic activity in the liver persisted for longer in mice that received encapsulated OK-432 than in animals that received unencapsulated OK-432.

Conclusions: Because it has been shown that both NK and intTCR cells play an important role in tumour immunity, an increase in the number of such cells can be considered likely to have an increased antitumour effect. Encapsulated OK-432 elicited liver-specific augmentation of cytotoxic activity and the effect was more persistent than that produced by OK-432 given in the conventional form; therefore, it may be useful for the treatment of tumours, particularly those arising in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Cells, Cultured
  • Drug Carriers
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Liposomes
  • Liver / immunology*
  • Liver Neoplasms / drug therapy
  • Mice
  • Phenotype
  • Picibanil / administration & dosage*
  • Picibanil / pharmacology
  • Receptors, Antigen, T-Cell / drug effects*
  • Receptors, Antigen, T-Cell / immunology
  • Streptococcus pyogenes

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Receptors, Antigen, T-Cell
  • Picibanil