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

17 Apr 2024
Treatment for first clinical trial patient with gamma delta CAR T for bone metastatic prostate cancer

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 metastasised 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, utilises gamma delta T cells to target a tumour 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 recognise 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 tumours 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 recognise and destroy tumours.

In addition to eliminating tumours, 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 tumours,” 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.   

Source: H. Lee Moffitt Cancer Center & Research Institute