81000140

open access

Version of Record

Preclinical Safety Pharmacology Study of a Novel Protein-Based Cancer Vaccine CHP-NY-ESO-1

English (英語)

The Kobe journal of the medical sciences

54(1)

23-34

Kobe University School of Medicine

2008

2008-02-20

CHP-NY-ESO-1 is a novel therapeutic cancer vaccine consisting of a recombinantprotein 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 waspreviously conducted, and the adverse events related to this drug were observed to belimited to skin reactions at injection sites. To further establish the safety ofCHP-NY-ESO-1, we studied the effects of its subcutaneous injection on vital functionssuch as the central nervous system, cardiovascular system and respiratory system usingpreclinical animal models. The effects of CHP-NY-ESO-1 on the cardiovascular systemwere investigated in dogs using a telemetry system for blood pressure and heart rateand the Holter monitoring for ambulatory electrocardiograms. No drug-relatedchanges were observed in these parameters. The effect of CHP-NY-ESO-1 on thehERG-dependent potassium currents was also examined using in vitro cultured cellsystem, and no inhibition of hERG currents was observed. The effects ofCHP-NY-ESO-1 on the central nervous system were examined in rats using functionalobservational battery method, and no drug-related changes were observed in homecage observations, open field observations, hand held observations, and perception andmotor function observations. The effect of CHP-NY-ESO-1 on the respiratory systemwas investigated in rats by measuring tidal volume, minute volume and respiratory rateusing whole-body plethysmograph method, and no significant changes were found inthese parameters. These results indicate that CHP-NY-ESO-1 would not have anypharmacological effects on vital functions and support the safety of this cancer vaccinefor clinical use.

safety pharmacology

紀要論文