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Restoration of Cytolytic T-Lymphocyte Response with a New Immunopotentiator, N-{4-[(4-Fluorophenyl)sulfonyl]phenyl}acetamide (CL 259,763), in Mice

Laboratory of Tumor Immunology, Chemotherapy Research Department, Medical Research Division, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965

The immunorestorative characteristics of a novel synthetic immunomodulator, N-{4-[(4-fluorophenyl)sulfonyl]phenyl}acetamide (CL 259,763), has been investigated in several experimental models. In one situation, the compound was shown to enhance the induction of a cytolytic T-lymphocyte response to the murine MBL-2 leukemia implanted in its syngeneic host in which only a minimal reactivity to the tumor is normally displayed. In a Vaccinia virus model, the compound similarly augmented the lytic activity of cytolytic T-lymphocyte to virus-infected targets in not only viral antigen-primed but also cyclosporin A-impaired mice. Likewise, the alloreactive cytolytic T-lymphocyte activity was recovered in animals immunocompromised by inoculation with murine plasmacytomas or cytoreductive anticancer drugs, such as cyclophosphamide and 5-fluorouracil. Thus, the present findings suggest that CL 259,763 is effective in potentiating the immune response to weak antigens as well as in restoring alloreactivity by sparing the immunotoxicity associated with the administration of cytotoxic drugs and the growth of neoplasms.

¹ To whom requests for reprints should be addressed, at Lederle Laboratories, Building 60B, Room 209, Pearl River, New York 10965.

Received 9/ 1/87. Revised 11/18/87. Revised 1/12/88. Accepted 1/22/88.