Autologous Priming Antigen-inducible Anti-PSMA CAR T-cells AB-3028

**Semantic type:** Cell|Pharmacologic Substance

**Definition:** A preparation of autologous T-lymphocytes that have been modified to encode a genetic circuit consisting of a priming receptor that induces the expression of a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) prostate-specific membrane antigen (PSMA) upon binding to an as of yet undisclosed priming antigen expressed on prostate cancer tumor cells, and a microRNA-adapted short hairpin RNA (shRNA-miR) module targeting Fas (FAS; CD95; APO-1; tumor necrosis factor receptor superfamily member 6; TNFRSF6) and human transforming growth factor beta (TGF-beta) receptor II (TGFbRII; TGFBR2), with potential immunomodulating and antineoplastic activities. Upon administration, autologous priming antigen-inducible anti-PSMA CAR T-cells AB-3028 target and bind to the priming antigen expressed on prostate cancer tumor cells, and induce the expression of anti-PSMA CAR, thereby killing PSMA-expressing tumor cells. The downregulation of the expression of Fas by the shRNA-miR prevents Fas-mediated apoptosis of the AB-3028 T-cells in the tumor microenvironment (TME). The downregulation of the expression of TGFbRII abrogates TGF-beta-mediated immunosuppression in the TME. PSMA is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells as well as in a variety of other tumors, including renal cell carcinomas. AB-3028 T-cells have also been engineered to include a constitutive synthetic pathway activator that promotes the persistence of the T-cells.

**Synonyms:** - AB 3028 - AB-3028 - AB3028 - Autologous Logic-gated Anti-PSMA CAR T Cells AB-3028