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益生菌引导的靶向实体瘤 CAR-T 细胞

英文原题:Probiotic-guided CAR-T cells for solid tumor targeting.

查看英文原题

Probiotic-guided CAR-T cells for solid tumor targeting.

PubMed 2023/10/12(内容时间) Science Q1 · IF 47.3(JCR 2025)

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中文摘要

靶向肿瘤抗原的疗法(如嵌合抗原受体(CAR)T细胞)面临的一项主要挑战,是在异质性实体瘤中找到特异且均一表达的合适靶点。相比之下,某些细菌可选择性定植于免疫豁免的肿瘤核心区域,并可工程化为不依赖抗原的治疗递送平台。为结合这两种策略,研究人员开发了益生菌引导CAR-T 细胞平台(ProCAR):定植于肿瘤的益生菌释放合成靶标,在肿瘤组织原位标记细胞,使CAR-T 能够介导裂解。该系统在多种人和小鼠癌症异种移植及同系模型中,均可安全有效地激活CAR-T 细胞并实现不依赖天然肿瘤抗原的细胞裂解。研究人员还进一步工程化构建多功能益生菌,使其同时释放趋化因子,以增强CAR-T 细胞募集和治疗应答。

展开英文摘要原文

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery.

To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers.

We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.

论文信息

作者
Vincent RL、Gurbatri CR、Li F、Vardoshvili A、Coker C、Im J、Ballister ER、Rouanne M
单位
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.United States
期刊
Science (New York, N.Y.)2023 Oct 13
原文标识
PubMed 37824640 · DOI 10.1126/science.add7034