February 3, 2014 | by Hiu Chung So
Although prostate cancer is often highly treatable, the prognosis for men with metastatic disease remains grim. According to the American Cancer Society, men with distant prostate cancer metastases have a five-year survival rate of 28 percent, and almost 30,000 men die from the disease each year in the United States.
Researchers hope to turn that tide by using two novel agents developed at City of Hope that will attack cancerous cells with the patient's own immune system. And thanks to a $1 million Movember-Prostate Cancer Foundation Challenge Award, this immunotherapy project can continue its preclinical progress for the next two years, with in-human trials beginning in early 2016.
Prior research at City of Hope and other institutions found that numerous cancer cells — including those of prostate cancer — activate a protein called STAT3 to evade the immune system and to promote their own growth and spread. In one arm of the new project, Marcin Kortylewski, Ph.D., assistant professor at City of Hope’s Department of Cancer Immunotherapeutics and Tumor Immunology, will be designing a unique agent — a nucleotide-based drug that delivers a small, interfering RNA called CpG-STAT3 — to inhibit STAT3 activity, thus stripping the cancer’s ability to grow and dodge the immune system, while simultaneously bolstering the patient’s own anti-tumor immunity.
In another arm of the project, Christine Brown, Ph.D., City of Hope’s group leader in T cell therapy preclinical research, and Saul Priceman, Ph.D., assistant research professor, will be extracting T cells and engineering them to specifically target and attack prostate cancer cells.
The reprogrammed T cells will then be administered on their own and alongside the anti-STAT3 agent to test their effectiveness in fighting prostate cancer. Ultimately, researchers hope, the combination of the two agents will mount a three-way strike that halts the tumor’s spread, breaks down the cancer’s anti-immunity barriers and directs an immunological assault against the cancerous cells throughout the body.
“Our proposed studies comprise a novel combined approach that will help release the brakes that are placed on the immune system by the cancer and also improve our genetically modified T cell therapy for patients with advanced-stage prostate cancer,” said Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope and the principal investigator of the project. “If successful, our approach will create a powerful immune response against prostate cancer, with the potential to better treat and possibly cure this disease.”
In a press release announcing the award, Movember and Prostate Cancer Foundation are equally enthusiastic about the project's potential.
“We believe that engineered T cell therapy for the treatment of advanced prostate cancer will be the next life-prolonging therapy. We are delighted to include Dr. Forman’s team and treatment discovery program at City of Hope in the Prostate Cancer Foundation’s portfolio of research excellence,” said Howard R. Soule, Ph.D., chief science officer and executive vice president of the Prostate Cancer Foundation.
"This financial aid, raised by our generous community of Mo Bros and Mo Sistas, will be used to accelerate the progress towards reducing the number of deaths and suffering due to recurrent or advanced prostate cancer," said Mark Hedstrom, director of Movember U.S.
Other City of Hope researchers involved in this study include Sumanta Pal, M.D., assistant professor in the Department of Medical Oncology & Therapeutics Research, and Joycelynne Palmer, Ph.D., senior biostatistician and hematological malignancies section head in the Department of Research Information Sciences.
Learn more about this and other research in Forman's laboratory here.