Type I NKT, also known as invariant NKT (iNKT) cells express a semi-invariant TCR and have several unique properties that make them well-suited for CAR-T therapy over conventional T cells. Since these T cells are not MHC-restricted, but instead recognize antigens presented by nonpolymorphic CD1d molecules, they are almost entirely devoid of alloreactivity. Thus, iNKT cells can be used as allogeneic, off-the-self therapy.
iNKT cells can directly kill cancer cells that express CD1d and NKG2D ligands through their endogenous invariant TCR (iTCR) or NKG2D. They infiltrate into tumor tissues rapidly and remodel the tumor microenvironment by selectively eliminating tumor-associated macrophage (TAM) and promoting myeloid-derived suppressor cell (MDSC) maturation into functional antigen-presenting cells (APCs). They can also promote dendritic cell maturation and cross-presentation of tumor-associated antigens to bystander T cells, thus inducing long-lasting memory T cell responses.
There are some perceived advantages of CAR-iNKT cell therapy over CAR-T cell therapy:
