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用于神经胶质瘤的下一代抗原呈递细胞免疫治疗。

Next-generation antigen-presenting cell immune therapeutics for gliomas.

机构信息

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Malnati Brain Tumor Institute, Chicago, Illinois, USA.

出版信息

J Clin Invest. 2023 Feb 1;133(3):e163449. doi: 10.1172/JCI163449.

Abstract

Antigen presentation machinery and professional antigen-presenting cells (APCs) are fundamental for an efficacious immune response against cancers, especially in the context of T cell-centric immunotherapy. Dendritic cells (DCs), the gold standard APCs, play a crucial role in initiating and maintaining a productive antigen-specific adaptive immunity. In recent decades, ex vivo-differentiated DCs from circulating CD14+ monocytes have become the reference for APC-based immunotherapy. DCs loaded with tumor-associated antigens, synthetic peptides, or RNA activate T cells with antitumor properties. This strategy has paved the way for the development of alternative antigen-presenting vaccination strategies, such as monocytes, B cells, and artificial APCs, that have shown effective therapeutic outcomes in preclinical cancer models. The search for alternative APC platforms was initiated by the overall limited clinical impact of DC vaccines, especially in indications such as gliomas, a primary brain tumor known for resistance to any immune intervention. In this Review, we navigate the APC immune therapeutics' past, present, and future in the context of primary brain tumors.

摘要

抗原呈递机制和专业抗原呈递细胞(APC)对于针对癌症的有效免疫反应至关重要,尤其是在以 T 细胞为中心的免疫治疗的背景下。树突状细胞(DC)作为标准的 APC,在启动和维持有效的抗原特异性适应性免疫中发挥着关键作用。在过去的几十年中,来自循环 CD14+单核细胞的体外分化 DC 已成为基于 APC 的免疫治疗的参考。负载肿瘤相关抗原、合成肽或 RNA 的 DC 可激活具有抗肿瘤特性的 T 细胞。这一策略为替代抗原呈递疫苗策略的发展铺平了道路,例如单核细胞、B 细胞和人工 APC,这些策略在临床前癌症模型中显示出了有效的治疗效果。替代 APC 平台的寻找是由 DC 疫苗的总体临床效果有限引发的,特别是在脑胶质瘤等适应症中,脑胶质瘤是一种已知对任何免疫干预均有抵抗力的原发性脑肿瘤。在这篇综述中,我们将探讨 APC 免疫治疗在原发性脑肿瘤背景下的过去、现在和未来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce8/9888388/413278555e37/jci-133-163449-g094.jpg

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