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Lorus uncovers antitumor mechanism of Virulizin

Lorus Therapeutics has published peer-reviewed results from the company's studies on the mechanism of its lead anticancer candidate, Virulizin, which acts by stimulating the host's intrinsic antitumor immunity.

The research suggests Virulizin activates the innate immune system of the host. Previous studies have shown that Virulizin induces the antitumor activity of macrophages, and that natural killer (NK) cells play a role in the antitumor efficacy of Virulizin.

Consolidating previous findings, this study demonstrates that NK cells play a crucial role in the antitumor activity of Virulizin, as NK cells isolated from Virulizin-treated mice had increased cytotoxicity against NK-sensitive cells and human melanoma cells, but not against NK-insensitive cells.

Depletion of NK cells in mice by an anti-NK specific antibody significantly compromised the antitumor activity of Virulizin. NK cell-mediated antitumor activity appears to rely on the activation of macrophages by Virulizin, further enhancing tumor killing effects.

It was found that IL-12, a key NK cell stimulatory factor, was involved in NK cell activation in vivo. IL-12 was significantly increased in macrophages isolated from Virulizin-treated mice. Levels of IL-12 alpha and IL-12 beta mRNA were increased in both peritoneal macrophages and in tumor xenografts as a result of increased numbers of macrophages following Virulizin treatment. In addition, the level of IL-12 beta was also substantially elevated in the serum of mice treated with the drug.

The results indicate that Virulizin induces macrophage IL-12 production, which in turn induces NK cell-mediated antitumor activity.

Virulizin is currently in a fully-enrolled pivotal phase III clinical trial for the treatment of pancreatic cancer. The drug has produced promising efficacy and safety data in several phase I and II clinical trials in Canada and the USA. It has also demonstrated excellent anticancer activity in a variety of preclinical human tumor models including pancreatic cancer, melanoma, breast cancer, ovarian cancer and prostate cancer.