Preclinical safety pharmacology study of a novel protein-based cancer vaccine CHP-NY-ESO-1.

CHP-NY-ESO-1 is a novel therapeutic cancer vaccine consisting of a recombinant protein of cancer antigen NY-ESO-1 and a polysaccharide-based delivery system, cholesteryl pullulan. A pilot clinical study of CHP-NY-ESO-1 in cancer patients was previously conducted, and the adverse events related to this drug were observed to be limited to skin reactions at injection sites. To further establish the safety of CHP-NY-ESO-1, we studied the effects of its subcutaneous injection on vital functions such as the central nervous system, cardiovascular system and respiratory system using preclinical animal models. The effects of CHP-NY-ESO-1 on the cardiovascular system were investigated in dogs using a telemetry system for blood pressure and heart rate and the Holter monitoring for ambulatory electrocardiograms. No drug-related changes were observed in these parameters. The effect of CHP-NY-ESO-1 on the hERG-dependent potassium currents was also examined using in vitro cultured cell system, and no inhibition of hERG currents was observed. The effects of CHP-NY-ESO-1 on the central nervous system were examined in rats using functional observational battery method, and no drug-related changes were observed in home cage observations, open field observations, hand held observations, and perception and motor function observations. The effect of CHP-NY-ESO-1 on the respiratory system was investigated in rats by measuring tidal volume, minute volume and respiratory rate using whole-body plethysmograph method, and no significant changes were found in these parameters. These results indicate that CHP-NY-ESO-1 would not have any pharmacological effects on vital functions and support the safety of this cancer vaccine for clinical use.