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.