Autologous PSMA-inducible Anti-CA9 CAR T-cells AB-2100 - CISMeF
Autologous PSMA-inducible Anti-CA9 CAR T-cells AB-2100NCIt concept
Preferred Label : Autologous PSMA-inducible Anti-CA9 CAR T-cells AB-2100;
NCIt synonyms : Autologous PSMA-inducible CA9 CAR T Cells AB-2100; Autologous PSMA x CA9 Logic-gated T-cells AB-2100; Autologous PSMA x CA9 Integrated Circuit T Cells AB-2100; Autologous PSMA x CA9 ICT Cells AB-2100;
NCIt 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) carbonic anhydrase
IX (CAIX; carbonic anhydrase 9; CA9; G250) upon binding to the TAA prostate-specific
membrane antigen (PSMA), 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 PSMA-inducible anti-CA9 CAR T-cells AB-2100 target and bind to PSMA expressed
on tumor cells and in tumor-associated neovasculature, and induce the expression of
anti-CA9 CAR, thereby killing PSMA- and CA9-expressing tumor cells. The downregulation
of the expression of Fas by the shRNA-miR prevents Fas-mediated apoptosis of the AB-2100
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. CA9
is a member of the carbonic anhydrase family that is found in a majority of renal
cell carcinomas while absent in most normal tissues. AB-2100 T-cells have also been
engineered to include a constitutive synthetic pathway activator that increases signal
transducer and activator of transcription 3 (STAT3) signaling, thereby promoting T-cell
cytotoxicity and expansion.;