Modulation of the immune response to tumors by a novel synthetic compound, (4R)-3-benzoyl-N-[(1R)-1-phenylethyl]-4-thiazolidinecarboxamide (RS-0481).

Abstract

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 tumor-specific 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.

• Authors: S Kurakata, M Tomatsu, M Arai, H Arai, A Hishinuma, H Kohno, K Kitamura, T Kobayashi, K Nomoto
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 33 Issue 2 Pg. 71-9 ( 1991) ISSN: 0340-7004 [Print] Germany
• PMID: 1828007 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Colony-Stimulating Factors
• Interleukin-2
• Thiazoles
• Thiazolidines
• RS 0481

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Bone Marrow (drug effects)
• Colony-Stimulating Factors (biosynthesis, pharmacology)
• Female
• Hypersensitivity, Delayed
• Interleukin-2 (biosynthesis, pharmacology)
• Killer Cells, Natural (drug effects)
• Macrophage Activation (drug effects)
• Mice
• Mice, Inbred C3H
• Neoplasm Metastasis
• Neoplasms, Experimental (immunology)
• T-Lymphocytes (drug effects)
• T-Lymphocytes, Cytotoxic (drug effects)
• T-Lymphocytes, Regulatory (drug effects)
• Thiazoles (pharmacology)
• Thiazolidines