Allogeneic iPSC-derived CD58KO Anti-MICA/MICB CAR-ADR-expressing T-cells FT836

**Semantic type:** Cell|Pharmacologic Substance

**Definition:** A preparation of allogeneic, off-the-shelf (OTS), T-lymphocytes derived from a clonal master induced pluripotent stem cell (iPSC) line, engineered and multiplex-edited to express both a chimeric antigen receptor (CAR) specific for the alpha 3 domain of the natural-killer group 2, member D receptor protein (NKG2D or KLRK1) ligands MHC class I polypeptide-related sequence A (MICA) and B (MICB) and an alloimmune defense receptor (ADR) targeting CD137 (4-1BB; tumor necrosis factor receptor superfamily member 9; TNFRSF9), in which adhesive ligand lymphocyte function-associated antigen 3 (LFA-3; CD58) is knocked out (CD58KO), with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic iPSC-derived anti-MICA/MICB CAR T-cells FT836 specifically target and bind to MICA/MICB-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. MICA and MICB are stress-induced NKG2D ligands overexpressed on infected cells and many cancer cell types, but are not expressed on most normal, healthy cells. The shedding of the alpha 1 and alpha 2 domains of MICA and MICB from the tumor cell surface allows the tumor cells to evade NKG2D-expressing immune cells. FT836 specifically targets the alpha 3 domain of MICA/B to overcome this shedding and tumor escape mechanism. The ADR targets 4-1BB, which promotes the elimination of 4-1BB+ alloreactive immune cells by the CAR T-cells, and enhances the persistence of the CAR T-cells. CD58 plays an important role in synapse formation and CD58KO leads to reduced adhesion thereby enhancing rejection resistance and the persistence of the CAR T-cells.

**Synonyms:** - Allogeneic iPSC-derived Anti-MICA/MICB CAR T Cells FT836 - Allogeneic iPSC-derived Anti-MICA/MICB CAR T-cells FT836 - Allogeneic iPSC-derived Anti-MICA/MICB CAR-T Cells FT836 - FT 836 - FT-836 - FT836