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(I,C)-LC] in the treatment of MBL-2 tumor ascites. Tumor-bearing mice received an optimal therapeutic protocol [100 micrograms poly(I,C)-LC administered twice a wk], a maximum tolerated dose [50 micrograms poly(I,C)-LC administered daily], or the optimal immunomodulatory protocol for normal mice [10 micrograms poly(I,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(I,C)-LC for immunomodulation in tumor-bearing animals are also the optimal therapeutic protocol but have less toxicity than the maximum tolerated dose.
D000818:Animals; D001201:Ascites / Q000473:pathology; D002266:Carboxymethylcellulose Sodium; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000166:cytology; D007111:Immunity, Cellular; D007167:Immunotherapy; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D010529:Peritoneal Cavity / Q000166:cytology; D011070:Poly I-C / Q000008:administration & dosage* / Q000633:toxicity; D011107:Polylysine / Q000008:administration & dosage*; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D011107:Polylysine; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C