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Immunomodulatory Effects in Mice of Polyinosinic-Polycytidylic Acid Complexed with Poly-L-lysine and Carboxymethylcellulose¹

Preclinical Screening Laboratory, Program Resources, Incorporated [J. E. T., J. A., H. P., M. C., B. L., M. S.], and Biological Response Modifiers Program [E. S., R. R., R. H. W., M. A. C.], National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland 21701

In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.

¹ Research sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract N01-23910 with Program Resources, Inc.

² To whom requests for reprints should be addressed.

³ Supported by a grant from Deutsche Forschungsgemeinschaft.

Received 5/ 7/84. Accepted 11/26/84.