Rearming Immune Cells Proves Successful in Treating Ovarian Cancer in Mice Trials

Ovarian cancer is such a deadly disease because it turns off the immune cells that try to fight it. Researchers and medical teams have been working tirelessly to find ways to reactivate immune cells after they’ve but shut down by ovarian cancer.

A Weill Cornell Medical College team recently discovered that disarming the gene XBP1 awakens and rearms the immune cells that successfully combat ovarian cancer. Here’s what else they had to say:

In Cell, the team reported that ovarian cancer, in later, liquified stages, oozes about inside the body, creating a toxic tumor microenvironment rife with damaging, reactive oxygen molecules. These molecules prompt the endoplasmic reticulum stress response pathway to turn on the XBP1 gene in dendritic cells (DCs). This prompts lipids to build up inside DCs and render them unable to do their job, which is to engulf cancer bits (antigen) and show them to T cells for attack.

The team is creating drugs to block XBP1 in both cancer and dendritic cells. For the paper, they injected nanoparticles, carrying a genetic molecule (siRNA) that blocks XBP1, into an ovarian cancer mouse model. DCs, seeing the nanoparticles as foreigners, ingested them. Once inside the DCs, like soldiers in a Trojan Horse, the nanoparticles swarmed out, and turned XBP1 off. This freed the dendritic cells to get to work warning T cells about the cancer.

“Probably the most important and clinically relevant finding in the paper is a demonstrated opportunity to therapeutically silence XBP1 in DCs to improve the development of antitumor immune responses,” Michael Shurin, M.D., Ph.D. (ABMLI) told Bioscience Technology. Shurin, University of Pittsburgh Medical Center Clinical Immunopathology associate director, was uninvolved in the work.

“Using nanodelivery of specific siRNA to silence the XBP1 gene of DCs in vivo, the authors demonstrated a significant reduction of tumor burden and tumor progression in mice, mediated by increased activity of tumor-specific cytotoxic T cells. These data provide a new target in key antigen-presenting cells in the tumor milieu to develop a therapeutic approach to ovarian cancer,” Shurin said.

Noted Louisiana State University tumor immunologist Paulo Rodriguez, Ph.D., to BioscienceTechnology: “Interestingly, deletion of XBP1 resulted in significant anti-tumor effects, and a dramatic transformation of tumor-associated DCs, from cells that promoted tumor growth, into populations that induced anti-tumor responses through activation of T cells.” Rodriguez was also uninvolved in the study. “These results emphasize the relevance of tumor-induced stress signaling on suppression of protective immune responses in cancer, a field that has generated significant attention over the last years.”

For the full article from Bioscience Technology, click here: http://www.biosciencetechnology.com/articles/2015/07/rearming-immune-cells-blasts-ovarian-cancer-mice