The capacity of α-galactosylceramide (α-GalCer) to act as an anti-cancer agent in mice through the specific stimulation of type I NKT (iNKT) cells has prompted extensive investigation to translate this finding to the clinic. However, low frequencies of iNKT cells in cancer patients and their hypo-responsiveness to repeated stimulation have been seen as barriers to its efficacy. Currently the most promising clinical application of α-GalCer, or its derivatives, is as stimuli for ex vivo expansion of iNKT cells for adoptive therapy, although some encouraging clinical results have recently been reported using α-GalCer pulsed onto large numbers of antigen presenting cells (APCs). In on-going preclinical studies, attempts to improve efficacy of injected iNKT cell agonists have focussed on optimising presentation in vivo, through encapsulation in particulate vectors, making structural changes that help binding to the presenting molecule CD1d, or injecting agonists covalently attached to recombinant CD1d. Variations on these same approaches are being used to enhance the APC-licencing function of iNKT cells in vivo to induce adaptive immune responses to associated tumour antigens. Looking ahead, a unique capacity of in vivo-activated iNKT cells to facilitate formation of resident memory CD8⁺ T cells is a new observation that could find a role in cancer therapy.

通过特异性刺激I型NKT（iNKT）细胞，α-半乳糖苷神经酰胺（α-GalCer）在小鼠中充当抗癌药的能力促使进行了广泛的研究，以将这一发现转化为临床应用。然而，癌症患者中iNKT细胞的低频及其对重复刺激的反应不足已被视为其功效的障碍。目前，最有希望的临床应用是α-GalCer或其衍生物，作为刺激iNKT细胞体外扩增以进行过继治疗的方法，尽管最近已报道了使用α-GalCer脉冲处理大量抗原呈递细胞的一些令人鼓舞的临床结果（APC）。在正在进行的临床前研究中，提高注射的iNKT细胞激动剂功效的尝试集中在优化展示上。在体内，通过封装在颗粒载体中，进行结构改变以帮助与呈递分子CD1d结合，或注射与重组CD1d共价连接的激动剂。这些相同方法的变异被用于增强iNKT细胞在体内的APC许可功能，以诱导对相关肿瘤抗原的适应性免疫反应。展望未来，体内激活的iNKT细胞具有促进驻留记忆CD8 ⁺ T细胞形成的独特能力，这是一项新发现，有望在癌症治疗中发挥作用。