Preclinical efficacy of Virulizin in human breast, ovarian and prostate tumor models.
Virulizin is a novel biological response modifier (BRM) approved for the treatment of melanoma and is currently in a phase III clinical trial against advanced pancreatic cancer. The purpose of this study was to define the anti-cancer activity of Virulizin against a number of solid human tumors. The therapeutic effect of Virulizin was evaluated in mouse xenograft models, and the results demonstrate that Virulizin has high efficacy against breast, ovarian and prostate tumor xenografts. Seventy-seven percent inhibition, with an optimal T/C value of 24.8%, was observed in human beast MDA-MB-231 xenografts treated with Virulizin as compared to saline-treated controls (p=0.0004). In human ovarian SK-OV-3 tumor xenografts, administration of Virulizin inhibited tumor growth by 77.6% compared to saline controls (p=0.0439). Furthermore, high anti-tumor activity was also demonstrated in DU145 and PC-3 prostate tumor xenografts, as indicated by 72.6 and 49.1% suppression of tumor growth (versus saline controls, p=0.0007 or p=0.0049), respectively. Direct comparisons with the anti-tumor activities of conventional drugs demonstrated that Virulizin has higher or equal efficacy against all four tumors tested. Finally, addition of Virulizin into co-cultures of tumor cells and macrophages stimulated the cytolytic activity of the macrophages against the tumor cells in a dose-dependent manner. This result suggests that stimulation of immune cells is at least part of the anti-tumor mechanism of action of Virulizin. These results clearly demonstrate that Virulizin inhibits the growth of human breast, ovarian and prostate tumors, indicating great potential for expansion of the clinical indications for this novel BRM.
Du
Caigan
C
R & D Department, Lorus Therapeutics Inc, Toronto, Ontario, Canada.
Feng
Ningping
N
Jin
Hongnan
H
Wang
Ming
M
Wright
Jim A
JA
Young
Aiping H
AH
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001646:Bile; D001943:Breast Neoplasms / Q000188:drug therapy*; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014020:Tissue Extracts; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D014020:Tissue Extracts; C087098:virulizin