Generation of tumoricidal effector cells with a novel potentiator: N-[4-[(4-fluorophenyl)sulfonyl]phenyl] acetamide (CL 259,763).
An effort was made to investigate the effects of a novel immunopotentiator, N-[4-[(4-fluorophenyl)sulfonyl]phenyl]acetamide (CL 259,763), on the generation of tumoricidal effector cells. It was demonstrated that a single oral dose of the compound (100-600 mg/kg) induced in mice a population of peritoneal macrophages capable of inhibiting the growth of tumor cells. These activated macrophages released proteases which seemed responsible for the tumor cell inhibition because the cytostatic activity was abrogated in the presence of protease inhibitors TLCK and aprotinin. On the other hand, addition of catalase and exogenous arginine to the culture failed to alter the effect, suggesting that hydrogen peroxide and arginase did not participate in this system. Although induction of cytolytic T-lymphocytes (CTL) reactive with syngeneic tumor cells was achievable in mice previously sensitized to the tumor, treatment with CL 259,763 rendered these animals even more responsive to tumor antigens resulting in a significant enhancement of tumor cell destruction. The compound was effective in augmenting the CTL response over a rather broad dose range of 25-200 mg/kg. In contrast to these stimulatory effects, the cytolytic activity of natural killer cells seemed not to be affected by the compound. Taken together, CL 259,763 is an orally active immunomodulator capable of inducing tumor inhibitory macrophages and potentiating CTL responses to syngeneic tumor cells and, therefore, may prove clinically useful in the treatment of neoplastic diseases.
Wang
B S
BS
Chemotherapy Research Department, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
Lumanglas
A L
AL
Lin
Y I
YI
Durr
F E
FE
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D013450:Sulfones; C048816:CL 259763