PSCA as a novel CAR T target for resistant prostate cancer

August 20, 2019 | by City of Hope

Prostate stem cell antigen (PSCA) is strongly expressed in about 90 to 100% of prostate cancer primary and metastatic specimens, at levels many-fold higher than in normal prostate tissue. Because of this and the near complete lack of expression in normal tissues, PSCA is a great candidate for targeted immunotherapy. Our experts are studying the potential effect of PSCA-targeted CAR T cell therapy for advanced prostate cancer treatment.
                       
PSCA-CAR T cells are created from a patient’s own T cells, which are engineered to kill cells that express PSCA. This is done by using a virus to insert a fragment of DNA into the immune cells, allowing them to recognize prostate tumor cells. In this phase 1 trial, the safety and tolerability of autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes are studied in adult patients with PSCA+ metastatic castration-resistant prostate cancer (mCRPC). The principal investigator is Tanya Dorff, M.D., an associate clinical professor in the Department of Medical Oncology & Therapeutics Research, who directs the Genitourinary Cancers Program at City of Hope.
 
Patients will receive a single infusion while in the hospital; the dose of T cells will be increased. Some of the patients in the trial will receive preconditioning chemotherapy with cyclophosphamide alone or with additional fludarabine.
 
While the potential for PSCA-CAR T to eradicate tumors in patients with mCRPC is not yet clear, the in vitro experiments have shown promising results similar to successes with CAR T therapy in other solid tumors. This study seeks to assess safety and optimal dosage by monitoring the disease response at various doses and adjusting based on any side effects identified.
 
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