Moffitt treats first clinical trial patient with gamma delta CAR T for bone metastatic prostate cancer

(Press-News.org) TAMPA, Fla. — Moffitt Cancer Center has treated its first patient in an investigator-initiated, phase 1 clinical trial investigating the safety and efficacy of a chimeric antigen receptor T-cell (CAR T) therapy for prostate cancer that has metastasized to the bone. Roughly 90% of men with advanced prostate cancer will develop bone metastases. The disease significantly impacts patients, causing extreme bone pain.

The CAR T-cell therapy, developed in the lab of Moffitt immunologist Daniel Abate-Daga, PhD, utilizes gamma delta T cells to target a tumor biomarker highly expressed in bone metastatic prostate cancer called prostate stem cell antigen. While many CAR T therapies employ alpha beta T cells, gamma delta T cells, which represent less than 5% of all T cells in the body, have unique biological properties that allow them to recognize a broader range of antigens through their T cell receptor, including molecules typically associated with stressed or infected cells, such as cancer. Most importantly, gamma delta T cells are unique in that they are most efficient when combined with a drug (zoledronate) that is commonly used to protect the bone in patients with bone metastatic cancer. 

In preclinical studies, Abate-Daga’s lab showed that the gamma delta CAR T cells significantly decreased the size of tumors and improved survival with limited toxicity. Additionally, pretreatment with zoledronate, a medication that helps strengthen bones, activated the CAR T cells through a CAR-independent mechanism, allowing for increased ability to recognize and destroy tumors. In addition to eliminating tumors, the treatment also preserves the health of the bones, as reported last year in a joint publication with the Conor Lynch, PhD, lab.

“We are hopeful that this therapy will help patients with prostate cancer and that this study will be just the first step towards the effective treatment of other bone tumors,” said Abate-Daga, whose lab developed the therapy in early 2023.

This is a single-center phase 1 dose-escalation trial with a 3+3 design. In a 3+3 design, three patients are enrolled into a cohort for a given dose. If no dose-limiting toxicities exist in the cohort, the trial enrolls additional participants into the next higher dose cohort. Patients with end-stage prostate cancer with no standard of care options left would be potential candidates for this study.

Jingsong Zhang, MD, PhD, medical oncologist in the Genitourinary Oncology Department at Moffitt, is the principal investigator for this phase 1 trial. Potential participants and referring physicians can learn more about the trial here.

Patients enrolled in the trial will have their T cells harvested through apheresis. The gamma delta T cells will then be engineered in Moffitt’s cell therapies core, adding the chimeric antigen receptor. The new CAR T cell will then be expanded to the hundreds of millions. Before infusion, patients will receive lymphodepletion chemotherapy to make room for the new cells. The process from cell collection to infusion will average 14 days.   

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 56 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. 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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