Virulizin-2gamma, a novel immunotherapeutic agent, in treatment of human pancreatic cancer xenografts.
Virulizin-2gamma, a novel biological response modifier extracted from bovine bile, has shown in clinical studies a significant antitumor activity against pancreatic cancer. We report here the results of preclinical evaluation of Virulizin-2gamma in treatment of human pancreatic cancer xenograft in nude mice. In this in vivo study, 14 daily bolus intraperitoneal administrations of Virulizin-2gamma (0.2 ml/mouse/day) significantly inhibited the growth of BxPC-3 human pancreatic tumor xenografts, with T/C value of 60%. Virulizin-2gamma 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-2gamma, either as a single agent or when combined with gemcitabine were found. Virulizin-2gamma was well tolerated by the mice. The data from in vitro studies revealed that Virulizin-2gamma did not have direct cytotoxicity against cultured tumor cell lines, indicating that the in vivo antitumor activity is likely due to its immunomodulating effects on host immune cells. These preclinical results supported the safety and efficacy observed in clinical studies and indicated that Virulizin-2gamma is a promising immunotherapeutic agent for treatment of pancreatic cancer and worthy of further clinical evaluation.
Liu
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Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-6395, USA.
Ferdinandi
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Ely
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Joshi
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001646:Bile; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014020:Tissue Extracts; D000093542:Gemcitabine
D000276:Adjuvants, Immunologic; D007155:Immunologic Factors; D014020:Tissue Extracts; C087098:virulizin; D003841:Deoxycytidine; D000093542:Gemcitabine