研究动态
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Toll样受体(TLR)及其激动剂在癌症疫苗和免疫治疗中的应用。

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy.

发表日期:2023
作者: Samik Chakraborty, Juan Ye, Herui Wang, Mitchell Sun, Yaping Zhang, Xueyu Sang, Zhengping Zhuang
来源: Frontiers in Immunology

摘要:

Toll 样受体 (TLR) 是在各种免疫细胞类型中表达的模式识别受体 (PRR),在诱导先天性和适应性免疫中发挥多种作用和职责。它们传播免疫力的能力使它们成为扩展众多针对癌症的免疫治疗方法的有吸引力的目标。这些免疫治疗策略包括使用 TLR 配体/激动剂作为单一疗法或联合治疗策略。多种 TLR 激动剂在高级临床试验中已证明具有显着疗效。近年来,多项报告证实了 TLR 激动剂作为化疗药物、放疗和免疫疗法(包括癌症疫苗)佐剂的适用性。癌症疫苗是癌症免疫治疗领域相对较新的方法,目前正在对治疗不同癌症进行广泛的评估。在本综述中,我们试图对重要的 TLR 激动剂进行包容性讨论,并讨论了它们的应用以及将其纳入癌症免疫治疗方法的挑战,特别强调了 TLR 激动剂作为癌症疫苗功能佐剂的用途。最后,我们介绍了 rWTC-MBTA 疫苗接种的转化潜力(用吞噬激动剂甘露聚糖-BAM、TLR 配体和抗 CD40 激动抗体脉冲的辐照全肿瘤细胞 (rWTC)),这是一种利用膜结合甘露聚糖-BAM 的自体癌症疫苗,以及 TLR 激动剂作为多种癌症类型的可能免疫疗法的免疫诱导能力。版权所有 © 2023 Chakraborty、Ye、Wang、Sun、Zhang、Sang 和 Zhuang。
Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in various immune cell types and perform multiple purposes and duties involved in the induction of innate and adaptive immunity. Their capability to propagate immunity makes them attractive targets for the expansion of numerous immunotherapeutic approaches targeting cancer. These immunotherapeutic strategies include using TLR ligands/agonists as monotherapy or combined therapeutic strategies. Several TLR agonists have demonstrated significant efficacy in advanced clinical trials. In recent years, multiple reports established the applicability of TLR agonists as adjuvants to chemotherapeutic drugs, radiation, and immunotherapies, including cancer vaccines. Cancer vaccines are a relatively novel approach in the field of cancer immunotherapy and are currently under extensive evaluation for treating different cancers. In the present review, we tried to deliver an inclusive discussion of the significant TLR agonists and discussed their application and challenges to their incorporation into cancer immunotherapy approaches, particularly highlighting the usage of TLR agonists as functional adjuvants to cancer vaccines. Finally, we present the translational potential of rWTC-MBTA vaccination [irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists Mannan-BAM, TLR ligands, and anti-CD40 agonisticAntibody], an autologous cancer vaccine leveraging membrane-bound Mannan-BAM, and the immune-inducing prowess of TLR agonists as a probable immunotherapy in multiple cancer types.Copyright © 2023 Chakraborty, Ye, Wang, Sun, Zhang, Sang and Zhuang.