Changes in cellular components of spleen and lymph node cells and the effector cells responsible for Meth A tumor eradication induced by zinostatin stimalamer.
We reported previously that pretreatment with zinostatin stimalamer (ZSS) eradicated Meth A tumors in BALB/c mice. We herein investigated cellular components of spleen and lymph node cells of Meth A-bearing ZSS-pretreated mice by flow cytometry; the antitumor effector cells by in vivo depletion of T cells, NK cells, or macrophages; and host-mediated antitumor activity associated with ZSS treatment after tumor transplantation. ZSS given on day-3 transiently decreased the number of spleen cells. The percentage of T cells increased, but B cells and macrophages decreased. B cells decreased in inguinal lymph nodes in Meth A-bearing ZSS-pretreated mice, but increased in Meth A-bearing control mice. In vivo depletion experiments using antibodies or carrageenan showed that antitumor effector cells for tumor eradication are Thy1.2+/Lyt2.2+ and that at least a part of them are asialo GM1+. Thy1.2+/Lyt2.2+/asialoGM1- cells are important in generation of the antitumor activity of ZSS; however, L3T4+ T cells are also involved in initiation of tumor eradication. The result of ZSS treatment after tumor transplantation suggests that ZSS might exhibit antitumor activity by augementating host-mediated antitumor resistance, as well as its intrinsic cytocidal activity.
Masuda
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E
Molecular Medicine Research Labs, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Maeda
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H
D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008299:Maleic Anhydrides / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011137:Polystyrenes / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018800:Thy-1 Antigens / Q000032:analysis; D013997:Time Factors; D009353:Zinostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D008299:Maleic Anhydrides; D011137:Polystyrenes; D018800:Thy-1 Antigens; C035755:poly(maleic acid-styrene)neocarzinostatin; D009353:Zinostatin