Dissociation of Therapeutic and Toxic Effects of Polyinosinic-Polycytidylic Acid Admixed with Poly-L-lysine and Solubilized with Carboxymethyl Cellulose in Tumor-bearing Mice

In this paper, we describe a study of the therapeutic parameters (dose and schedule) and immunomodulatory activity (macrophage, natural killer cell, and T-cell number and function) of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose [poly(l,C)-LC] in the treatment of MBL-2 tumor ascites. Tumor-bearing mice received an optimal therapeutic protocol [100 µg poly(l,C)-LC administered twice a wk], a maximum tolerated dose [50 µg poly(l,C)-LC administered daily], or the optimal immunomodulatory protocol for normal mice [10 µg poly(l,C)-LC administered daily]. The percentage of tumor-associated macrophages and their cytotoxic activity correlated with host survival. In addition, splenic T-cell activity correlated with host survival, and splenic natural killer cell function had a near significant correlation with host survival. These results indicate that the optimal dose and schedule of poly(l,C)-LC for immunomodulation in tumor-bearing animals are also the optimal therapeutic protocol but have less toxicity than the maximum tolerated dose.