Antitumor mechanisms of Z-100, 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 Z-100, 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 of lymphocytes isolated from Z-100-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 Z-100 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 10(6) cells) and lymphocytes (2 x 10(5) cells) derived from Z-100-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sasaki
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H
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Schmitt
D
D
Hayashi
Y
Y
Pollard
R B
RB
Suzuki
F
F
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D007267:Injections; D007377:Interleukin-3 / Q000096:biosynthesis; D008055:Lipids / Q000302:isolation & purification / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008351:Mannans / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007377:Interleukin-3; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama