Hao Cui , Yu-Yue Zhao , Yan-Hua Han , Zhou Lan , Ke-Long Zou , Guo-Wang Cheng , Hao Chen , Pei-Liang Zhong , Yan Chen , Li-Min Ma , Tong-Kai Chen , Guang-Tao Yu
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引用次数: 0
Abstract
Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique.
Statement of significance
F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.
肿瘤与淋巴结之间的交流对抗肿瘤免疫疗法具有重要意义。重塑肿瘤引流淋巴结(TdLN)的免疫微环境对提高免疫疗法的抗肿瘤能力起着关键作用。在这项研究中,我们构建了一种由装载效应记忆T(TEM)细胞和PD-1抑制剂(aPD-1)的F127水凝胶组成的生物仿生人工淋巴结结构。生物仿生淋巴结有助于将 TEM 细胞和 aPD-1 运送到 TdLN 和肿瘤免疫微环境中,从而实现有效、持续的抗肿瘤免疫疗法。利用 TEM 细胞独特的凝胶形成和降解特性,冷肿瘤通过补充 TEM 细胞迅速转化为热肿瘤。同时,与传统给药方法相比,aPD-1 的疗效显著提高。我们的研究结果表明,F127@TEM@aPD-1 的开发有望成为未来新型临床给药技术。F127@TEM@aPD-1皮下注射后,可向肿瘤引流淋巴结(TdLN)和肿瘤微环境持续补充TEM细胞和aPD-1,不仅能通过缓释提高ICB的疗效,还能对肿瘤和TdLN产生双重调控作用。
期刊介绍:
Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.