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Induction of Tumor Immunity and Natural Killer Cell Cytotoxicity in Mice by 5-Halo-6-phenyl Pyrimidinone¹

Department of General Surgery, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute [E. L., C. A. S.], Houston, Texas 77030; Department of Biological Structure, University of Washington [S. P.], Seattle, Washington 98195; and Smith, Kline & French Laboratories [N. H.], Swedeland, Pennsylvania 19479

We have investigated the effect of pyrimidinone molecule 2-amino-5-iodo-6-phenyl-4 pyrimidinone (AIPP) on natural killer (NK) cell lytic potential and on the growth of ascitic mammary adenocarcinoma, ACA-755, in B6D2F₁ mice. Our studies demonstrated that AIPP was effective in both the prophylaxis and the therapy of this tumor and that the antitumor effect was mediated via induction of NK cell lytic activity. In vitro characterization studies showed that the AIPP-induced cytotoxic cells were not macrophages and exhibited characteristics of NK cells such as morphology of the large granular lymphocytes and sensitivity to asialo GM-1 antibody. Analysis of the mechanism of potentiation of NK cell cytotoxic function by AIPP indicated that the enhancement of cytotoxicity was accomplished by recruitment of NK cell tumor-binding potential (primarily those with large granular lymphocytic morphology) as well as by increased frequency of lytic NK cells. These studies implicate NK cells in the defense against malignant tumors and suggest that regional therapy with AIPP may represent a new therapeutic modality for treatment of cancer.

¹ This work was supported by Grants CA 31394, CA 39632, and CA 32553 awarded by the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 12/10/85. Revised 4/21/86. Accepted 6/30/86.