Effect of tumor burden and route of administration on the immunotherapeutic properties of polyinosinic-polycytidylic acid stabilized with poly-L-lysine in carboxymethyl cellulose [Poly(I,C)-LC].
We examined the immunomodulatory and therapeutic activities of poly(I,C)-LC. Mice received a subcutaneous (s.c.) injection of sufficient numbers of MBL-2 lymphoma cells to produce in 1 week either a high or low tumor burden. A week after tumor cell injection, poly(I,C)-LC treatment was initiated; the agent was administered intraperitoneally (i.p.) at 5 mg/kg twice a week or at 2.5 or 0.5 mg/kg every day or as an intravenous (i.v.) injection at 0.5, 0.05, or 0.005 mg/kg three times a week. Poly(I,C)-LC treatment significantly increased antitumor effector cell functions in a variety of organs (including spleen, lungs, and peritoneum), as shown by increased killing of MBL-2 cells in vitro and increased tumor cell killing by natural killer cells and macrophages. Furthermore, prolongation of survival correlated with peritoneal macrophage tumoricidal activity when poly(I,C)-LC was given i.p. and with pulmonary effector cell function (including natural killer, cytolytic T-lymphocyte and macrophage tumoricidal activity) when the agent was administered i.v.
Black
P L
PL
Division of Antiviral Drug Products, U.S. Food and Drug Administration, Rockville, MD 20857.
Hartmann
D
D
Pennington
R
R
Phillips
H
H
Schneider
M
M
Tribble
H R
HR
Talmadge
J E
JE
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000031:analogs & derivatives; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011107:Polylysine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000031:analogs & derivatives; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C