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Urdu“Bone metastatic prostate cancer is an incurable disease that significantly impacts patient lives through extreme bone pain,” said study co-lead author Conor Lynch, Ph.D., interim chair of the Tumor Biology Department at Moffitt. “Bisphosphonates such as zoledronate help mitigate this problem and reduce pathological fracture but have little impact on patient survival. Therefore, new treatment options are urgently needed.”
Moffitt researchers wanted to investigate the possibility of using CAR T-cell therapy for bone metastatic prostate cancer and whether this treatment approach could be enhanced by combining it with zoledronate. CAR T therapy is relatively new in cancer treatment. This form of cellular immunotherapy was first approved in 2017 for certain blood cancers. For this therapy, T cells isolated from patients are genetically engineered to target a tumor-specific marker. The T cells are expanded in culture and infused back into the patient where they can target tumor cells for destruction.
In this collaborative study between the labs of Lynch and Daniel Abate-Daga, Ph.D., co-first authors Jeremy Frieling, Ph.D., and Leticia Tordesillas, Ph.D., used a specific subtype of T cell called gamma/delta T cells.
“These are relatively less studied than the conventional alpha/beta T cells but have attracted substantial interest from the biotech sector in recent years,” said co-lead author Abate-Daga, associate member of the Department of Immunology and scientific director of the Cell Therapies Core Facility at Moffitt.
The researchers created CAR T cells that were specific to the tumor biomarker called prostate stem cell antigen (PSCA) that is highly expressed in bone metastatic prostate cancer. They demonstrated that the CAR T cells killed prostate cancer cells in cell culture and stimulated the production of chemical messengers that stimulate immune cell activity.
They next moved their experiment to mouse models and showed that the CAR T cells significantly decreased the size of tumors and improved survival with limited toxicity. Additionally, pretreatment of the mice with zoledronate helped activate the CAR T cells through a CAR-independent mechanism, allowing for increased ability to recognize and destroy tumors. Importantly, in addition to eliminating tumors, this treatment was able to preserve the health of the bones.
“To our knowledge, this study is the first to evaluate gamma/delta T cells for expressing chimeric antigen receptor and treating bone metastatic prostate cancer. This strategy offers a dual-targeting mechanism to eradicate bone metastatic prostate cancer, a strategy that can be quickly translated to the clinical setting,” Abate-Daga said.
The study was supported by the National Cancer Institute (P30CA07629, R01CA241169 and U01CA244101), Department of Defense Prostate Cancer Research Program (W81XWH-18-2-0013, W81XWH-18-2-0015, W81XWH-18-2-0016, W81XWH-18-2-0017, W81XWH-18-2-0018 and W81XWH-18-2-0019) and a team science award from Moffitt Cancer Center.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 53 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 7,800 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube.
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