Effect of lipid-arabinomannan (z-100) on the growth of human cervical carcinoma in scid mice inoculated with human lymphocytes

Antitumor activities of Z-100, an itnmunopotentiator extracted from M. tuberculosis, has been shown in man and animais bearing various malignancies. In the present study the influence of Z-100 on the growth of xenogeneic tumors (human SiHa cervical carcinoma cells, SiHa cells) in SCID mice inoculated with peripheral blood lymphocytes (PBL) from healthy volunteers were examined. SCID mice (BALB/c origin) inoculated with PBL (1 x 107 cells/mouse, i.v.) from healthy volunteers (hu-PBLSCID mice) were implanted with SiHa cells (2 x 106 cells/mouse, s.c., 3 days after PBL inoculation). Then, they were treated s.c. with a mixture of IL-4 (100 ng/mouse) and IL-10 ( 100 ng/mouse) every 5 days in combination with or without Z-100 (Zeria Pharmaceutical Co., Ltd., Tokyo, Japan, 0.1 100 fig/kg, s.c.) every other day beginning one day after tumor inoculation. Xenogeneic SiHa cells were completely eliminated in hu-PBL-SCID mice. However, SiHa cells inoculated in hu-PBL-SCID mice grew, at the same levels observed in SCID mice treated with saline, when mice were treated with a mixture of type 2 cytokines. When tumor-bearing hu-PBL-SCID mice received the mixture of type 2 cytokines in combination with Z-100, at doses of 1-100 (ig/kg, 71-89% of the tumor growth was suppressed, as compared with the tumor growth in hu-PBL-SCID mice treated with only type 2 cytokines. These doses of Z-100 did not show any antitumor activities to SiHa cells directly in vivo and in vitro. These results suggest that Z-100 may have a potential on the protective immunity influenced by type 2 cytokines in cancer patients.