KIR-based CAR T cells

KIR-based CAR T cells (also known as cKIR-CAR T cells) represent a novel approach to chimeric antigen receptor (CAR) design that mimics the multichain architecture of natural killer (NK) cell receptors. Developed by researchers at the University of Pennsylvania, these cells express a chimeric killer immunoglobulin-like receptor (cKIR) fused to an extracellular antigen-binding domain. Unlike conventional CARs that use a single-chain CD3-zeta signaling domain, cKIRs associate with the ITAM-containing adaptor protein DAP12 to initiate signaling. Recent research has also identified a DAP12-independent signaling pathway where the cytoplasmic tail of KIR2DS2 recruits the adaptor protein GRB2 to activate the Ras/MAPK pathway. This dual-signaling mechanism results in enhanced cytotoxicity, increased production of cytokines like IFN-gamma, and superior anti-tumor efficacy in solid tumor models compared to traditional CAR T cell designs.

Other names

cKIR-CAR T cellschimeric killer immunoglobulin-like receptor CAR T cellscKIR-modified T cells