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CAR-iNKT is a chimeric antigen receptor (CAR) modified invariant natural killer T (iNKT) cell therapy. iNKT cells are rare innate lymphocytes that bridge innate and adaptive immunity, recognizing lipid antigens presented by CD1d. This therapy leverages the inherent properties of iNKT cells, such as their protective effect against acute-graft-versus-host-disease (aGVHD) and their potential as an off-the-shelf CAR immunotherapy platform. Preclinical evidence suggests that CAR-iNKT cells may outperform CAR-T cells against blood cancers like B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma. A key advantage of CAR-iNKT cells is their high expression of VLA-4 (comprising ITGA4 and ITGB1), which mediates adhesion to endothelial cells and facilitates trafficking across the blood-brain barrier (BBB) and into the central nervous system. This enhanced trafficking is particularly relevant for treating leptomeningeal leukemia, a common complication of B-ALL. CAR-iNKT cells are engineered with CARs to target specific cancer antigens, such as CD19/CD133 for B-ALL or BCMA for multiple myeloma, combining targeted cytotoxicity with superior migratory capabilities.
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