Compound class: Synthetic organic

Comment: AH10-7 is a sphinganine α-galactosylceramide (or galactosylsphingamide) that has been designed for the potential to activate CD1d-restricted invariant natural killer T (iNKT) cells as a mechanism to augment immune responses against cancer and infections [1]. It is an analogue of KRN7000 (PubChem CID 2826713, a.k.a. α-GalCer) that was originally developed for its potent immunomodulatory effects, and which was investigated as an immuno-oncology agent [3,7]. However, KRN7000 induces both Th1 and Th2 cytokine production, and produces a suboptimal immune response, which likely accounts for its apparent limited efficacy in clinical trials [5,8]. AH10-7 overcomes KRN7000's unpredictable effects by promoting a Th1-biased immune response, which suggests that it will elicit more favorable results against cancer and infection (whereas a Th2-biased response would likely be of more benefit against autoimmune diseases). Both KRN7000 and AH10-7 are ligands for the lipid-binding MHC class I-like protein CD1d. Recognition of lipid-based antigens presented by CD1d sets iNKT cells apart from conventional T cells.
Van Kaer and Wu (2018) have published a review of the therapeutic potential of iNKT cells in autoimmune conditions [6] and the application of unconventional T cells in immuno-oncology is reviewed by Godfrey et al. (2018) [2] and Krijgsman et al. (2018) [4].