ABSTRACT

Introduction: Heat-labile enterotoxins (HLTs) and their cognate ganglioside receptors have been extensively studied because of their therapeutic potential. Gangliosides play arole in modulating effector cells of the immune system, and HLTs provide a novel means for stimulating ganglioside-mediated responses in immunocompetent cells.

Areas covered: To evaluate the mechanisms of HLT adjuvanticity, a systemic literature review was performed using relevant keyword searches of the PubMed database, accessing literature published as recently as late 2020. Since HLTs bind to specific ganglioside receptors on immunocytes, they can act as regulators via stimulation or tapering of immune responses from associated signal transduction events. Binding of HLTs to gangliosides can increase proliferation of T-cells, increase cytokine release, augment mucosal/systemic antibody responses, and increase the effectiveness of antigen presenting cells. Subunit components also independently stimulate certain immune responses. Mutant forms of HLTs have potent immunomodulatory effects without the toxicity associated with holotoxins.

Expert opinion: HLTs have been the subject of abundant research exploring their use as vaccine adjuvants, in the treatment of autoimmune conditions, in cancer therapy, and for weight loss, proving that these molecules are promising tools in the field of immunotherapy.

摘要

简介: 耐热肠毒素 (HLT) 及其同源神经节苷脂受体因其治疗潜力而被广泛研究。神经节苷脂在调节免疫系统的效应细胞中发挥作用，而 HLT 为刺激免疫活性细胞中神经节苷脂介导的反应提供了一种新方法。

涵盖的领域：为了评估 HLT 佐剂性的机制，使用 PubMed 数据库的相关关键字搜索进行了系统的文献综述，访问了最近在 2020 年底发表的文献。由于 HLT 与免疫细胞上的特定神经节苷脂受体结合，它们可以充当调节剂通过刺激或逐渐减少来自相关信号转导事件的免疫反应。HLT 与神经节苷脂的结合可以增加 T 细胞的增殖，增加细胞因子的释放，增加粘膜/全身抗体反应，并增加抗原呈递细胞的有效性。亚基成分也独立地刺激某些免疫反应。突变形式的 HLT 具有强大的免疫调节作用，而没有与全毒素相关的毒性。

专家意见：HLT 已成为大量研究的主题，探索其作为疫苗佐剂、治疗自身免疫性疾病、癌症治疗和减肥的用途，证明这些分子是免疫治疗领域有前途的工具。