Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.
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.
Talmadge
J E
JE
Adams
J
J
Phillips
H
H
Collins
M
M
Lenz
B
B
Schneider
M
M
Schlick
E
E
Ruffmann
R
R
Wiltrout
R H
RH
Chirigos
M A
MA
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
D000276:Adjuvants, Immunologic; D007369:Interferon Inducers; D010455:Peptides; D011107:Polylysine; C019531:poly ICLC; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C