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].
