UPDATE: AB-3028 Reaches Clinical Trial Stage for mCRPC

AB-3028, programmable circuit T cell therapy for metastatic castration-resistant prostate cancer (mCRPC), has now advanced into a Phase 1/2 clinical trial. This marks the first clinical testing of this highly engineered, logic‑gated CAR-T platform in prostate cancer, moving it from a purely preclinical concept into human evaluation. The trial should start recruiting in January 2026.

We talked about this new therapy in a previous article but here is a brief explanation.

AB-3028 is built on a clear rationale: conventional CAR-T cells struggle in solid tumors because of off‑tumor toxicity, immunosuppressive signaling, and rapid T‑cell exhaustion. To address this, AB-3028 was engineered with a sequential “AND‑gate” design that requires recognition of PSMA plus a second priming antigen, so cytotoxic activity is focused on tumor cells co‑expressing both markers rather than healthy tissues with low‑level antigen expression.​

Beyond targeting, AB-3028 incorporates shRNA modules against FAS and TGFBR2 to reduce activation‑induced cell death and blunt TGF‑β–mediated suppression in the tumor microenvironment, while a synthetic JAK/STAT pathway activator sustains T‑cell function and limits exhaustion without relying on exogenous cytokines. Together, these “programmable circuit” elements are designed to enhance specificity, persistence, and functional fitness of the infused T cells, providing a mechanistic justification for testing AB-3028 in the new Phase 1/2 mCRPC trial.

The trial will assess safety, dosing, and preliminary efficacy of a single autologous infusion in PSMA‑positive, heavily pretreated mCRPC patients, using a Bayesian dose‑escalation design followed by expansion cohorts. If the program confirms acceptable safety and early activity, it could position AB-3028 as one of the first truly programmable cell therapies to demonstrate clinical benefit in advanced prostate cancer.

Clinical trial.