Prostate cancer remains a formidable challenge, particularly in its advanced stages, where bone metastases and treatment resistance dominate outcomes. At City of Hope, our focus is on leveraging immunotherapy to transform this landscape.
One promising avenue is prostate stem cell antigen (PSCA)-directed CAR T cell therapy. This approach, developed in collaboration with our translational research team, demonstrated durable responses against prostate cancer, including bone lesions. Moving this therapy into the clinic requires careful consideration of dosing, lymphodepletion and toxicity management. City of Hope’s first-in-human trial, published in Nature Medicine, underscored the importance of correlative science: Biopsies revealed CAR T cell infiltration and antigen expression, guiding refinements for future studies.
A key challenge in solid tumor CAR T cell therapy is persistence. Our early trials showed limited durability, prompting strategies to enhance the tumor microenvironment. Lymphodepletion improved antigen presentation and reduced immunosuppressive macrophages. Building on this, we are now investigating radiation as a priming agent in a phase IB trial, aiming to further augment CAR T cell activity.
Expanding beyond CAR T: bispecific T Cell engagers
In parallel, we are advancing bispecific T cell engager (BiTE) programs. These agents tether immune cells to cancer cells, eliciting potent cytotoxic responses. Managing unique toxicities, such as cytokine release syndrome, requires robust education and multidisciplinary coordination. Industry partnerships have accelerated these efforts, enabling prophylactic strategies and optimized trial design.
City of Hope’s integrated infrastructure — spanning manufacturing, regulatory expertise and clinical operations — has been instrumental in delivering these innovations safely. And as our national network continues to expand access to cutting-edge therapies, we are able to prioritize diversity in clinical trial enrollment.
Looking ahead
The future of prostate cancer care lies in bold translational steps. By connecting laboratory discoveries with clinical insights, City of Hope aims to achieve breakthroughs rather than incremental gains. With continued collaboration and investment, immunotherapy can redefine outcomes for patients facing prostate cancer.
City of Hope® is one of the largest and most advanced cancer research and treatment organizations in the U.S. To learn more about City of Hope, visit: www.cityofhope.org.
Discover City of Hope’s latest genitourinary cancer innovations on this “On the Edge of Breakthrough: Voices of Cancer Research” podcast episode and at City of Hope’s data presentations at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium happening Feb. 26-28 in San Francisco.
