A-CAR032: a STEAP2-Targeted Armored CAR-T Enters First-in-Human Trial for Advanced Prostate Cancer

A new Phase 1 clinical trial is testing A-CAR032, a CAR-T cell therapy, in patients with metastatic castration-resistant prostate cancer, or mCRPC. This first-in-human study targets STEAP2, a protein found on nearly all prostate cancer cells, including those that have spread to bones and lymph nodes.

Prostate cancer creates a tough environment for immune cells to fight it. The tumor surrounds itself with barriers that suppress the immune system. One major barrier is TGF-β, a signaling molecule made by cancer cells and surrounding tissues that weakens T cells and stops them from attacking tumors. A-CAR032 addresses this by adding a special “armor” to the CAR-T cells. This armor blocks TGF-β signals, letting the engineered T cells stay active and keep killing cancer cells even in the tumor’s hostile environment.

STEAP2 stands out as a target because it appears on more than 85% of prostate cancer cells from early tumors to late-stage metastases. Unlike some other prostate cancer proteins that disappear as the disease progresses, STEAP2 stays consistently present. Normal tissues have little STEAP2, mainly in the bladder, which reduces the risk of damaging healthy organs.

The therapy works by taking a patient’s own T cells, adding genes for a receptor that recognizes STEAP2 and the TGF-β armor, then growing billions of these modified cells and infusing them back. Before infusion, chemotherapy clears space for the CAR-T cells to expand. This approach has cured many blood cancers, and now tests if it can tackle the “immune cold” prostate cancer.

Clinical trial.