Prostate Cancer Awareness Month: Unlocking the Power of Immunotherapy to Combat a Common Men’s Cancer

Prostate cancer is the second most common for men, only trailing skin cancer. Approximately 1.3 million men are diagnosed with prostate cancer annually, and one in seven men will be impacted by it in their lifetime. Prostate cancer is a disease that can be managed and treated well if caught in the early stages, where the five-year survival rate is nearly 100 percent. However, if the cancer is not detected until it has spread, the five-year survival rate plummets to under 30 percent. 

Historically, immune checkpoint therapies have experienced a low response rate against prostate cancer. More recently, there has been encouraging data regarding T cell redirectors with prostate cancer that clinical trials have illuminated. T cell redirectors are a cancer treatment that uses engineered molecules to guide T cells directly to cancer cells, enhancing the immune system’s ability to target and destroy tumors. Through ongoing clinical trials, researchers are continuing to enhance immunotherapy for prostate cancer, aiming to further improve patient outcomes. 

CRI-Funded Scientists Discuss Challenges and Opportunities Against Prostate Cancer

Prostate cancer is not a one-size-fits-all disease. There are those that are very responsive to hormonal therapies with good prognosis and those that are considered ‘aggressive variants.’

Bilal Siddiqui, MD, CRI Clinical Innovator

Over the past 15 years, CRI-funded scientists have made several crucial discoveries in the fight against prostate cancer. Padmanee Sharma, MD, PhD, professor in the departments of Genitourinary Medical Oncology and Immunology, scientific director for the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center, co-director of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center, and CRI Scientific Advisory Council member, alongside Sumit Subudhi, MD, PhD, associate professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, and former CRI Cancer Vaccine Collaborative grantee, have conducted pioneering studies testing the immune responses of patients with advanced prostate cancer treated with a specific immune checkpoint therapy. 

Likewise, current CRI-funded scientists seek to further break down barriers between prostate cancer challenges and improve patient outcomes. Bilal Siddiqui, MD, assistant professor in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center and CRI Clinical Innovator, is a clinical/translational investigator and a medical oncologist. Dr. Siddiqui said he is focused on designing and conducting clinical trials for prostate cancer patients. 

“A major difference between prostate cancer and others that have been more responsive to immunotherapies is the former has a highly immunosuppressive tumor microenvironment, characterized by few infiltrating effector T cells, enrichment of suppressive immune cell population, suppressive signaling pathways, and stromal elements,” he told CRI. Dr. Siddiqui expressed optimism for T cell redirectors as a promising class of therapy, especially those that target the protein complex CD3 and the T cell receptor CD28. “I do not expect that these will be curative as monotherapies but anticipate they will form part of the treatment arsenal for this disease.” 

Other CRI-funded scientists that are looking to effectively target prostate cancer focus on a specific cellular immunotherapy called chimeric antigen receptor (CAR) T therapy, which can bind to antigens present on tumor cell surfaces where other treatments fail. Alexandra Bartlett, PhD, postdoctoral scholar at Oregon Health & Science University and CRI-Taylor Ann Scott Postdoctoral Fellow, echoed Dr. Siddiqui’s sentiment that the immunosuppressive tumor environment is a major barrier to CAR T cell therapy’s success against prostate cancer. Dr. Bartlett also said there is another roadblock to immunotherapy efforts against prostate cancer – the toxicity of treatments. 

“If the treatment is too toxic, it does not matter if it is effective at shrinking tumors,” she explained. Addressing treatment toxicity is at the focus of Dr. Bartlett’s research. “CAR T cells cannot differentiate between cancer and normal cells. In blood cancers, patients are given infusions to combat the effect of damage to healthy cells. However, when this happens in solid organs, major problems occur because you cannot replace those damaged cells.” 

She is currently using a mouse model to address this ‘on-target, off-tumor,’ toxicity that prostate cancer patients experience to develop nontoxic immunotherapy strategies. 

Conclusion: Prostate Cancer Symptoms, Screening, and FDA-Approved Immunotherapies 

According to Johns Hopkins Medicine, 85 percent of prostate cancer cases are diagnosed before patients exhibit symptoms. Common symptoms include frequent nighttime urination, pain experienced with urination, pain or stiffness from the lower back through the upper thighs, and more. A blood test or a routine rectal exam could reveal a patient’s prostate cancer. 

The U.S. Food and Drug Administration (FDA) has approved three immunotherapy treatments to bolster immunologists’ options against prostate cancer. One is a cancer vaccine and two are checkpoint inhibitors, which block the immune system’s ‘brakes’ that tumors can manipulate to inhibit a successful immunotherapy response to cancer. CRI scientists and the immunotherapy community at large are dedicated to thwarting this common malignancy in men and bringing us closer to a world immune to cancer.