α-GalCer, an α-Candidate in Tumour Suppression

Abstract

α-GalCer is well-known as an exogenous glycolipid mediator for potent iNKT response. 6,13 α-GalCer(Bf), an α-GalCer compound, is produced at various sites within humans, ABSTRACT Alpha-Galactosylceramide (α-GalCer, KRN7000) is an exogenous glycolipid ligand that is presented by CD1d molecules in antigen-presenting cells (APCs). It activates invariant natural killer T (iNKT) cells, characterized by semi-invariant T cell receptors (TCRs), which often leads to further downstream activation of the immune system. For example, iNKT cells release cytokines that regulate myeloid-derived suppressor cells (MDSCs) to promote tumor suppression. This critical review aims to clarify the observed effects of α-GalCer by examining recent studies, ranging from in vitro experiments with mice to in vivo clinical trials with humans. Within the current literature, α-GalCer has demonstrated beneficial effects toward tumour suppression. Most pre-clinical studies evaluating α-GalCer have seen success in suppressing tumour growth and increasing patient lifespan, although clinical trials yield inconclusive results. For example, the use of α-GalCer comes with severe limitations, including the induction of immune cell anergy amongst other unwanted side effects. Future studies and trials will be necessary to evaluate the full potential of α-GalCer. Nonetheless, α-GalCer may be a promising agent in combating cancer.