Phase I Study of PSMA-TGFβR DN CAR Modified T-cells in Patients with Advanced Castrate Resistant Prostate Cancer
About Phase I Study of PSMA-TGFβR DN CAR Modified T-cells in Patients with Advanced Castrate Resistant Prostate Cancer
- CAR T-cells are immune cells collected from a patient’s own blood and genetically engineered to recognize specific molecules expressed by tumor cells. When re-infused into the patient, these cells seek and kill tumor cells expressing the targeted molecule and can provide life-long tumor surveillance. This strategy has led to cures in lymphoma patients and has significant promise for the treatment of prostate cancer patients.
- Dr. Carl June and team are developing CAR T-cells that recognize and kill prostate cancer cells that can also resist immune suppression mechanisms.
- Patient T-cells will be transduced with a chimeric antigen receptor (CAR) gene engineered to recognize the prostate cancer-specific protein PSMA and with a dominant-negative receptor molecule for the immune-suppression protein TGF-β. When the CAR T-cells come into contact with a prostate cancer cell that expresses PSMA, the CAR molecule will bind to PSMA and send a signal to activate the T-cell to kill the tumor cell. When the CAR T-cell encounters TGF-β in the environment, the dominant-negative receptor will prohibit any normal TGF-β receptors expressed by the T-cell from suppressing T-cell activity.
- The efficacy and safety of this therapy will be tested in advanced castrate resistant prostate cancer patients in a phase 1 clinical trial. Patients will also be assessed for the functionality and continued persistence of the CAR T-cells over time, and whether CAR T-cell therapy influences other anti-tumor immune responses including antibody responses.
- Post-treatment biopsies will be obtained from some patients and evaluated to determine expression of PSMA by tumor cells and infiltration of the tumor with both CAR T-cells and unmodified T-cells.
- Finally, the levels of circulating tumor cells (CTCs) will be measured over time to determine if CTC levels reflect the efficacy of CAR T-cell therapy.
What this means for patients: CAR T-cell immunotherapy has demonstrated profound tumor-killing activity in lymphoma patients. Dr. June and team will create a CAR T-cell immunotherapy for prostate cancer patients and test it in clinical trials. If successful, this project will generate a powerful new therapy for the treatment of prostate cancer patients.
Carl June, MD (University of Pennsylvania)
Naomi Haas, MD (University of Pennsylvania), Marcela Maus, MD, PhD (University of Pennsylvania)