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稳定化 iRGD 修饰增强 NY-ESO-1 TCR-T 在实体瘤中的浸润并与 PD-1 阻断协同

英文原题:Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade.

PubMed 2025/05/30(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

研究概要

目前,癌症免疫治疗中的两个主要挑战通常阻碍了T细胞受体修饰T细胞(TCR-T)疗法在实体瘤治疗中的应用,包括T细胞浸润实体瘤组织的能力有限以及抑制T细胞抗肿瘤效能的免疫抑制信号。

中文摘要

目前,癌症免疫治疗中有两项主要挑战常限制T细胞受体修饰T细胞(TCR-T)疗法用于实体瘤:T细胞浸润实体瘤组织的能力有限,以及抑制T细胞抗肿瘤效能的免疫抑制信号。本研究构建了NY-ESO-1特异性TCR-T细胞,并引入聚乙二醇-磷脂(PEG-脂质),以非肽类九肽iRGD稳定修饰NY-ESO-1 TCR-T细胞,旨在增强其体内穿透能力;随后联合PD-1阻断以缓解免疫抑制信号。结果提示,以iRGD稳定修饰NY-ESO-1 TCR-T是一种简单有效的策略,可使TCR-T靶向并穿透实体瘤组织。此外,iRGD修饰的NY-ESO-1 TCR-T联合PD-1阻断,为治疗难治性NY-ESO-1阳性实体瘤提供了一种新的协同策略。

展开英文摘要原文

Currently, two main challenges in cancer immunotherapy commonly hinder the application of T cell receptor-modified T cell (TCR-T) therapy in the treatment of solid tumors, including the limited ability of T cells to infiltrate solid tumor tissues and the immunosuppressive signals that restrain the anti-tumor efficacy of T cells. In this study, we constructed NY-ESO-1-specific TCR-T and introduced polyethylene glycol-phospholipids (PEG-lipids) to stably modify NY-ESO-1 TCR-T with nonapeptide iRGD, aiming to enhance the penetrability of T cells in vivo, then we combined iRGD-modified NY-ESO-1 TCR-T (iRGD-NY-ESO-1 TCR-T) with PD-1 blockade to alleviate immunosuppressive signals. In result, it is suggested that stably modifying NY-ESO-1 TCR-T with iRGD is a simple and effective strategy to enable TCR-T to target and penetrate solid tumor tissues. Besides, the combination of iRGD-NY-ESO-1 TCR-T with PD-1 blockade presents a novel synergistic strategy for the treatment of refractory NY-ESO-1-positive solid tumors.

论文信息

作者
Wu Y、Qin L、Wang J、Xie Z、Su X、Li X、Yang Y、Huang R
第一作者单位
Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.China
通讯作者单位
Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China. zouzhengyun@njglyy.com.China
期刊
Cancer immunology, immunotherapy : CII2025 May 30
原文标识
PubMed 40445421 · DOI 10.1007/s00262-025-04077-1