title: Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.
abstract: 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.
authors.forename: J E
authors.initials: JE
authors.lastname: Talmadge
authors.forename: J
authors.initials: J
authors.lastname: Adams
authors.forename: H
authors.initials: H
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Collins
authors.forename: B
authors.initials: B
authors.lastname: Lenz
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: E
authors.initials: E
authors.lastname: Schlick
authors.forename: R
authors.initials: R
authors.lastname: Ruffmann
authors.forename: R H
authors.initials: RH
authors.lastname: Wiltrout
authors.forename: M A
authors.initials: MA
authors.lastname: Chirigos
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology* / Q000031:analogs & derivatives; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007369:Interferon Inducers / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology* / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D007369:Interferon Inducers; D010455:Peptides; D011107:Polylysine; C019531:poly ICLC; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C