Modulation of the immune response to tumors by a novel synthetic compound, (4R)-3-benzoyl-N-[(1R)-1-phenylethyl]-4-thiazolidinecarboxamide (RS-0481).
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.
Kurakata
S
S
Bio-Science Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Tomatsu
M
M
Arai
M
M
Arai
H
H
Hishinuma
A
A
Kohno
H
H
Kitamura
K
K
Kobayashi
T
T
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000494:pharmacology; D005260:Female; D006968:Hypersensitivity, Delayed; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D007376:Interleukin-2; D013844:Thiazoles; D053778:Thiazolidines; C069040:RS 0481