CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Probiotic-guided CAR-T cells for solid tumor targeting.
Probiotic-guided CAR-T cells for solid tumor targeting.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
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。
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.
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