Virulizin (R)-2 gamma, a novel immunotherapeutic agent, in treatment of human pancreatic cancer xenografts

Virulizin(R)-2 gamma, a novel biological response modifier extracted from b ovine bile, has shown in clinical studies a significant antitumor activity against pancreatic cancer. We report here the results of preclinical evalua tion of Virulizin-2 gamma in treatment of human pancreatic cancer xenograft in nude mice. In this in vivo study, 14 daily bolus intraperitoneal admini strations of Virulizin-2 gamma (0.2 ml/mouse/day) significantly inhibited t he growth of BxPC-3 human pancreatic tumor xenografts, with T/C value of 60 %. Virulizin-2 gamma also potentiated the antitumor activity of gemcitabine (120 mg/kg x4, q3d) in this tumor model. The combination therapy resulted in T/C values of 26% compared to gemcitabine alone (T/C 33%). In addition, based on body weight observation, no signs of toxicity related to treatment with Virulizin-2 gamma, either as a single agent or when combined with gem citabine were found. Virulizin-2 gamma was well tolerated by the mice. The data from in vitro studies revealed that Virulizin-2 gamma did not have dir ect cytotoxicity against cultured tumor eel lines, indicating that the in v ivo antitumor activity is likely due to its immunomodulating effects on hos t immune cells. These preclinical results supported the safety and efficacy observed in clinical studies and indicated that Virulizin-2 gamma is a pro mising immunotherapeutic agent for treatment of pancreatic cancer and worth y of further clinical evaluation.