Tumor-associated stress antigens (γδ TCR and NK receptor ligands)

The target profile 'Multiple tumor/stress antigens recognized via γδ TCR and NK-like receptors' describes the multi-ligand recognition system employed by gamma delta (γδ) T cells, particularly the 'Super Sentinel' platform developed by Adicet Bio (1). This recognition system utilizes a dual-receptor mechanism: the γδ T-cell receptor (TCR) identifies intracellular phosphoantigens (such as isopentenyl pyrophosphate) that are presented on the cell surface by butyrophilin proteins BTN3A1 and BTN2A1 (2, 3). Concurrently, innate-like natural killer (NK) receptors, such as NKG2D, detect stress-induced ligands including MICA, MICB, and ULBPs that are upregulated in malignant or infected cells (4, 5). This multi-antigen targeting allows for broad, MHC-independent anti-tumor activity across various cancers (6). Therapeutic candidates like ADI-001 and ADI-270 are engineered to exploit these natural sensing pathways to treat hematologic and solid tumors (7).

Other names

PhosphoantigensNKG2D ligandsStress-induced ligandsButyrophilin-presented antigensMICA/BULBPsγδ T-cell receptor ligands