[The significance of a combination of hepatic artery pump reservoir and new immunotherapy for cancer (NITC) in the treatment of colorectal liver metastasis].

Infusion of anti-cancer agents through a hepatic artery pump reservoir has been reported as a relatively useful means of treating multiple liver metastases but its mechanism of action remains to be clarified. We thought that immune responses might be involved in the mechanism of action of this therapy and attempted to test this assumption in patients with colorectal liver metastases. When the patients were divided into two groups by survival period (the 24-week or longer survival group and the less than 24-week survival group), the 24-week or longer survival group had significantly higher Th1 cytokine levels (p<0.001-0.05) and significantly lower VEGF levels (p<0.01) than the less than 24-week survival group. The survival rate tended to be higher in patients for whom intra-arterial infusion therapy was combined with NITC. These results suggest that the combined therapy induces some kind of immune reaction closely related to tumor size reduction and prolonged patient survival. It seems necessary to compare immune activity during intra-arterial infusion therapy alone with activity during intra-arterial infusion treatment in combination with a new immunotherapy.

[Significance of gefitinib combined with immunotherapy in tumor-bearing mice].

Gefitinib (brand name: Iressa) is a drug approved for molecule-targeting therapy in lung carcinoma patients. There are still many unresolved problems concerning the safety and mechanism of action of this drug. Based on the expectation that this drug combined with immunotherapy would be highly effective, we recently conducted an experiment in tumor-bearing mice. In this experiment, however, the tumor was not significantly reduced in size by this combined therapy. However, since the tumor in this animal model was EGFR positive and because tumor growth tended to be suppressed in mice with higher immune activity, it seems likely that additional studies of this therapy will contribute to identifying the optimum drugs to be combined with gefitinib and the optimum method of dosing that will lead to satisfactory efficacy and safety of gefitinib combined with immunotherapy.

H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts.

IL-12 is considered to be one of the most important cytokines in anti-cancer therapy. We have demonstrated that substances derived from Basidiomycetes, such as active hexose-correlated compound (AHCC) and PSK induce the production of IL-12. In this study, the MHC dependency of IL-12 production induced by various mycelial extracts, PSK, AHCC and IL-X, was examined. During tumor-bearing, higher serum IL-12 levels were observed in H-2a and H-2b mice as compared to H-2d mice. Concerning the effect of genetic background of mice on response to mycelial extracts, AHCC administration enhanced the serum IL-12 level in H-2b mice but not in H-2d mice, while PSK administration increased the serum IL-12 level in H-2d mice but not in H-2b mice. IL-X, components derived from the same Basidiomycetes, also enhanced the serum IL-12 level in H-2b mice in the early stage of tumor like AHCC, and maintained serum IL-12 at a level higher than the normal value accompanying tumor growth, whereas AHCC did not restore the lowered serum IL-12 level accompanying tumor growth. These results showed that AHCC or IL-X is effective in a genetically Th1-dominant individual whereas PSK is effective in a genetically Th2-dominant individual or Th2-dominant status in advanced cancer patients. So we propose that the suitable combinations of various mycelial extracts may be effective methods of endogenous IL-12 induction for cancer patients of all stages, which is important as a cancer therapy that is relatively free from adverse reactions and which emphasizes the QOL in individual patients.