NKT Ligand Conjugated Immunotherapy

Abstract

Vα14-NKT cells express an invariant TCR α-chain and restricted TCR β-chains using Vβ8, Vβ7, and Vβ2 and are restricted by CD1d molecule, which can present glycolipids such as α-galactosylceramide (α-GalCer) groups. The representative compound among α-GalCer ligands is KRN7000, which was chemically modified from natural agelasphins of marine sponge. KRN7000 had been originally screened by the using in vivo assays for anti-tumor effects, and was subsequently qualified as a ligand for Vα14-NKT cells. When Vα14-NKT cells are activated by α-GalCer-pulsed professional antigen-presenting cells, e.g. dendritic cells (DCs), they produce various cytokines such as IL-2, IL-4, IL-10, IL-13, IL-17, IL-21 and IFN-γ, which are involved in the immune regulation between innate and acquired immunity. And, IL-12 production from the α-GalCer-pulsed DC after the interaction with Vα14-NKT cells is beneficial to the attenuation of tumor progression and of Th2-dominant allergic diseases. In addition, a novel delivery of α-GalCer lipsomes to splenic B220+ cells makes it possible to induce regulatory cells in vivo, and to suppress the secondary antibody responses in mice. Accumulated results suggest that a wide variety of NKT ligand-conjugated immunotherapies can be accomplished by the precise delivery of α-GalCer to the target cells expressing CD1d.