Taking off the brakes to beat prostate cancer

March 24, 2016 | by City of Hope

Marcin Kortylewski, Ph.D., Jeremy Jones, Ph.D. and Sumanta Pal, M.D. Marcin Kortylewski, Ph.D., Saul Priceman, Ph.D., Sumanta Kumar Pal, M.D.

Researchers at City of Hope believe they are on the verge of significant headway in the treatment of advanced prostate cancer, thanks to new thinking and “staggering” early success.

This is a very exciting time for cancer therapy,” said assistant research professor Saul Priceman, Ph.D. “The progress we’ve made highlights the tremendous potential, still in its infancy, that’s yet to be realized.”

The need is clear. Localized prostate cancer has a five-year survival rate of nearly 99 percent, but when prostate cancer spreads throughout the body, the survival rate drops to 28 percent. The disease kills more than 26,000 men each year.

Much of the new excitement is focused on immunotherapy, especially T cells genetically engineered to produce chimeric antigen receptors, or CARs, which attack cancer cells with matching antigens. When researchers unleashed CAR-T cells on the CD19 antigen in leukemia and lymphoma, “the responses were so complete, it was staggering,” Priceman said. “There’s never been such a robust therapy for blood cancers.”

As a group leader in City of Hope’s T cell Therapeutics Research Laboratory, led by Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, Priceman’s mission is to achieve comparable success targeting harder-to-pinpoint antigens in solid tumors, particularly for prostate cancer. The team has identified an appropriate target, and a human clinical trial is projected for 2017.

“More and more people are coming to realize that cancer is, in fact, a disease of the immune system.” Said Marcin Kortylewski, Ph.D., associate professor in the Department of Immuno-Oncology. Leveraging that relatively new concept, Kortylewski and Priceman are working on a potential “double blow” attack plan, combining CAR-T cell treatment with a therapy that disrupts STAT3, a protein that’s known to suppress the immune system.

“You need to do more than just stimulate the immune system, if the system is dysfunctional. What we’re doing is taking off the brakes,” said Kortylewski.

Key to Kortylewski’s plan is a way to shut down STAT3’s cancer-promoting properties while turbocharging immune cells. Human clinical trials could begin as early as 2017.

Researchers have also applied new thinking to traditional hormone therapy. For decades, doctors have known about the link between prostate cancer and the testosterone-powered androgen receptor, which triggers cancer cell growth. Drugs that attack the receptor by suppressing testosterone levels eventually lose their effectiveness because cancer cells adapt to keep growing without testosterone.

Now, assistant professor Jeremy Jones, Ph.D., is working with a drug derived from pyrvinium that targets the androgen receptor independent of testosterone, killing cancer cells and preventing eventual resistance. Human clinical trials are estimated to be 18 months away, after Jones and his team develop a pill to deliver the normally insoluble pyrvinium molecule.

Jones and assistant professor Sumanta Pal, M.D., are also moving forward with perfecting the “liquid biopsy” capable of detecting tumor cells in the bloodstream, a much less invasive procedure compared to extraction biopsy of tumor tissue.

“We now have the technology to pull from blood some of the same information we would get form cancer tissue,” said Jones. “Anything we do in the lab,” said Jones, “must have a clear path toward helping patients as quickly as possible. That’s the purpose of our research.” 

 

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