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实体瘤中基于膜融合纳米颗粒的 HLA 肽靶向通用型 T 细胞受体工程化 T(HAUL TCR-T)细胞疗法

英文原题:Membrane fusogenic nanoparticle-based HLA-peptide-addressing universal T cell receptor-engineered T (HAUL TCR-T) cell therapy in solid tumor.

查看英文原题

Membrane fusogenic nanoparticle-based HLA-peptide-addressing universal T cell receptor-engineered T (HAUL TCR-T) cell therapy in solid tumor.

PubMed 2023/08/07(内容时间) Bioeng Transl Med Q1 · IF 6.2(JCR 2025)

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中文摘要

T细胞受体工程化T(TCR-T)细胞疗法已在基础研究和临床试验中显示治疗实体瘤的效果。由于TCR依赖肽抗原识别且受人白细胞抗原(HLA)限制,TCR-T疗法通常需针对个体抗原进行定制。缺乏适用于肿瘤细胞的通用靶点,显著限制了其临床应用。建立通用TCR-T治疗策略具有重要意义。本研究设计并评估了一种基于HLA-肽(pHLA)负载膜融合递送系统的通用HLA-肽寻址(HAUL)TCR-T疗法。该pHLA纳米颗粒(NP)肿瘤细胞膜修饰技术可借助膜融合性纳米颗粒,将pHLA转移至肿瘤细胞表面;随后由TCR-T细胞特异性识别并杀伤肿瘤细胞。HAUL TCR-T是一种通用技术,可使特异性TCR-T细胞识别并杀伤肿瘤细胞,而不受肿瘤细胞HLA分型影响。

展开英文摘要原文

T cell receptor-engineered T (TCR-T) cell therapy has demonstrated therapeutic effects in basic research and clinical trials for treating solid tumors. Due to the peptide-dependent recognition and the human leukocyte antigen (HLA)-restriction, TCR-T cell therapy is generally custom designed to target individual antigens. The lack of suitable universal targets for tumor cells significantly limits its clinical applications. Establishing a universal TCR-T treatment strategy is of great significance.

This study designed and evaluated the HLA-peptide-addressing universal (HAUL) TCR-T cell therapy based on HLA-peptide (pHLA) loaded membrance fusogenic deliver system. The pHLA-NP-based tumor cell membrane modification technology can transfer the pHLA onto the surface of tumor cells through membrane fusogenic nanoparticles.

Then tumor cells are recognized and killed by TCR-T cells specifically. The HAUL TCR-T cell therapy technology is a universal technology that enables tumor cells to be identified and killed by specific TCR-T cells, regardless of the HLA typing of tumor cells.

论文信息

作者
Xu R、Wang Q、Zhu J、Bei Y、Chu Y、Sun Z、Du S、Zhou S
单位
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing China.China
期刊
Bioengineering & translational medicine2023 Nov
原文标识
PubMed 38023696 · DOI 10.1002/btm2.10585