CURATIVE EFFECTS OF COMBINATION THERAPY WITH LENTINAN AND INTERLEUKIN-2 AGAINST ESTABLISHED MURINE TUMORS, AND THE ROLE OF CD8-POSITIVE T-CELLS

The antitumor activity of a combination of an antitumor polysaccharide , lentinan (a beta1-3 glucan with beta1-6 branches), and interleukin-2 (IL-2) was evaluated against established MBL-2 lymphoma and S908.D2 s arcoma at i.d. sites. Treatment of the MBL-2-tumor-bearing BDF1 mice w ith lentinan and IL-2 induced complete regression of tumor in 87.5% of mice treated. In contrast, treatments using either lentinan or IL-2 a lone failed to induce complete regression of tumor, although temporal growth inhibition of tumor was observed about in half of the mice trea ted. Improvements of antitumor effects by the combination of lentinan and IL-2 were also observed in the MBL-2/B6 and S908.D2/B10.D2 systems . Expression of the antitumor effects of lentinan/IL-2 treatments requ ired the intact T cell compartment, because the effects were not obser ved when nude mice were used. In the MBL-2/B6 system, the antitumor ac tion of lentinan/IL-2 treatment was abolished in mice treated with ant ibody to CD8 antigen, whereas antibodies to CD4 or NK 1.1 were ineffec tive. Furthermore, augmented tumor-specific cytotoxic T lymphocyte (CT L) activity was observed in regional lymph node cells of the mice afte r lentinan and IL-2 administration. These data indicate that the antit umor effects of lentinan/IL-2 are mediated by CD8+ CTL but not by CD4 T cells or NK1.1+ NK/LAK cells, and suggest that this combined therap y may be effective against even established tumors that are resistant to IL-2 therapy.