Immunotherapy for Prostate Cancer Combining Targeted Inhibition of STAT3-mediated Immunosuppression with CAR-engineered T-cells

About Immunotherapy for Prostate Cancer Combining Targeted Inhibition of STAT3-mediated Immunosuppression with CAR-engineered T-cells

Dr. Forman and his team will create a novel combination therapy that will empower a prostate cancer patient’s immune system to eliminate his cancer. T-cells are a specialized type of immune cell with extraordinary surveillance and cell-killing capabilities. Dr. Forman’s group will engineer a patient’s own T-cells to recognize and kill prostate cancer cells. This T-cell therapy, termed “chimeric antigen receptor (CAR) T-cells,” is a form of “live” therapy similar in principle to vaccination, in that once administered, T-cells can persist long term and provide ongoing tumor cell surveillance and protection from recurrence. To enhance the efficacy of these engineered T-cells, Dr. Forman’s group will deliver a second agent, “CpG-STAT3 siRNA,” that suppresses an immune-inhibiting and oncogenic protein, thereby simultaneously promoting T-cell activity while impeding tumor cell growth and survival mechanisms. This therapy will be tested in pre-clinical studies to benchmark efficacy and will ultimately be advanced into human clinical investigations. If successful, this project will lead to the development of a powerful immunotherapeutic treatment modality for prostate cancer patients.

What this means for patients: Although the immune system is the body’s potent natural defense against dangers, including invading bacteria and viruses, and internal upsets such as cancer cells, it has been historically and frustratingly difficult to create therapies that alter our immune system in a way that significantly slows prostate cancer growth. This is because successful tumors create an environment that inhibits the ability of the immune system to recognize and kill tumor cells. Dr. Forman’s team is developing a novel combination therapy approach that will, A) engineer a prostate cancer patient’s own immune system to recognize and kill cancer cells, and B) use RNA interference to limit the amount of a protein (STAT3) that is both an oncogene and blocks the immune system from becoming highly activated. These agents are expected to act together in synergy in altering a patient’s immune system while suppressing cancer cell growth in order to deliver a triple-knockout punch to prostate cancer cells. The researchers will do the necessary preclinical research on this combination therapy, and hope to bring these agents to clinical trials as early as 2016.

Principal Investigator:

Stephen J. Forman, MD (City of Hope)

Co-investigators:

Christine E. Brown, PhD (City of Hope), Marcin Kortylewski, PhD (City of Hope), Saul J. Priceman, PhD (City of Hope), Sumanta Pal, MD (City of Hope), Joycelynne Palmer, PhD (City of Hope)