Antitumor mechanisms of Z-10O, an immunomodulatory arabinomannan extracted from mycobacterium tuberculosis: The importance of lymphocytes infiltrated into tumor sites

The mechanisms of increased host resistance to tumors following treatment with Z-100, an arabinomannan extracted from mycobacterium tuberculosis, were investigated in mice bearing syngeneic solid tumors. When BALB/c mice bearing Meth-A solid tumors were treated intralesionally (i.l.) with a 10 mg/kg dose of Z100, 74% of tumor growth was inhibited in the test group as compared with control mice treated with saline. However, no significant tumor inhibitory activity was observed when these mice were treated with various doses of Z-100 i.p. or i.v. In addition, tumor growth in X-irradiated mice (450 R, whole-body irradiation) and in mice treated with antilymphocyte serum was not suppressed even though Z-100 was administered into the tumor. The number oflymphocytes isolated from Z100-treated tumor tissues increased 3.2-fold (14 days after the tumor inoculation), whereas no change in the number of tumor-infiltrating lymphocytes was demonstrated in mice treated with Z100 i.p. or i.v. as compared to controls. When BALB/c mice were inoculated s.c. with a mixture of Meth-A tumor cells (1 X 10⁶ cells) and lymphocytes (2 X 10⁵s cells) derived from Z1OO-treated tumor tissues in a Winn's neutralization test, decreased growth of solid tumors was demonstrated as compared with that of control mice inoculated with tumor cells alone. However, no such inhibition of tumor growth was observed in mice inoculated with a mixture of the tumor cells and lymphocytes obtained from tumor tissues of control mice at the same effector to target cell ratio. These results suggest that the antitumor activity of Z-100 administered i.l. against Meth-A solid tumors in BALB/c mice might be displayed through the activity of lymphocytes infiltrated into tumor tissues.