Preclinical SC and IV repeat-dose toxicology of a cowpea mosaic virus - A cancer immunotherapy candidate.

Cancer immunotherapies focus on boosting the immune system to recognize and eliminate tumor cells. Amongst the various biologics under development for cancer immunotherapy, our team has focused on the study of plant viruses in this context. We have shown that intratumoral administration of cowpea mosaic virus (CPMV) relieves the immunosuppressive tumor microenvironment and elicits a potent, systemic and durable anti-tumor immune response. The potency of CPMV has been demonstrated in several tumor mouse models and in companion canine cancer patients. Toward clinical development, we here studied the pharmacology and safety of CPMV. The repeat-dose toxicity of CPMV was evaluated in female Sprague Dawley rats. Rats received three weekly treatments (subcutaneous or intravenous) of a fixed dose (∼20 mg/kg), and complete necropsy was performed either 24 hrs (acute toxicity group) or 14 day (recovery group) post-dose. All animals reached the scheduled euthanasia times, and no clinical abnormalities were noted during the study period. Important clinical chemistry, hematology and histopathology findings included decreased albumin/globulin ratio, leukocytosis, neutrophilia, monocytosis, and lymphoid hyperplasia (Dunnett's test, p<0.05) - these changes support the immunostimulatory mode of action for CPMV. All other changes were considered mild, within historical range for the model, and/or not biologically significant. Neither a maximum tolerated dose (MTD) nor a no-observable adverse effect level (NOAEL) was established in this study. Overall, data indicate a good safety profile for the CPMV cancer immunotherapy candidate.