Modulation of the immune response to tumors by a novel synthetic compound, (4R)-3-benzoyl-N-[(1R)-1-phenylethyl]-4-thiazolidinecarboxamide (RS-0481) |
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Authors: | Shinichi Kurakata Mikiko Tomatsu Miyuki Arai Harumi Arai Atsushi Hishinuma Hiroko Kohno Kouichi Kitamura Tomowo Kobayashi Kikuo Nomoto |
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Affiliation: | (1) Bio-Science Research Laboratories, Sankyo Co. Ltd., Hiromachi 1-2-58, Shinagawa-ku, 140 Tokyo, Japan;(2) Research Institute, Sankyo Co. Ltd., 140 Tokyo, Japan;(3) Department of Immunology, Medical Institute of Bioregulation, Kyushu University, 812 Fukuoka, Japan |
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Abstract: | Summary RS-0481, (4R)-3-benzoyl-N-[(1R)-phenylethyl]-4-thiazolidinecarboxamide, is a compound that can re-establish the function of certain lymphoid cell populations impaired by the presence of a growing tumor in an animal. The compound markedly augmented the tumorspecific cytotoxic T lymphocytes,Tdth (delayed-type hypersensitivity T cells), and the nonspecific lymphokine-activated-killer-cell-like cell responses. It also enhanced the tumor-inhibitory effect of macrophages in tumor-bearing mice, but not in normal mice, indicating that it enhances the antitumor immune responses. Lymphocytes from RS-0481-treated tumor-bearing mice released significantly higher amounts of macrophage-activating factor(s) (MAF) and interleukin-2(IL-2)-like factors in culture compared with lymphocytes from untreated animals. Also, sera from treated tumor bearers showed elevated colony-stimulating factor (CSF) activity. Although the compound did not influence the factor-producing activity in mice without tumor, it enhanced the responsiveness of their bone marrow cells, T cells, and macrophages to CSF, IL-2, and MAF. It seems therefore possible that the compound enhances the responsiveness of immunocompetent cells to cytokines, resulting in a marked augmentation of antitumor T cell responses in tumor-bearing mice. Consistently it inhibited the development of lymph node metastasis of transplanted X5563 plasmacytoma, and we showed that T cells play a decisive role in this inhibition. The compound also counteracted the development of suppressor T cell activity in the spleen of tumor-bearing mice. |
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Keywords: | Tumor immunity X5563 plasmacytoma Biological response modifiers Thiazolidine immunomodulator Cytokine responsiveness |
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