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可植入 CAR T 细胞工厂增强实体瘤治疗。

Implantable CAR T cell factories enhance solid tumor treatment.

机构信息

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Biomaterials. 2024 Jul;308:122580. doi: 10.1016/j.biomaterials.2024.122580. Epub 2024 Apr 15.

Abstract

Chimeric Antigen Receptor (CAR) T cell therapy has produced revolutionary success in hematological cancers such as leukemia and lymphoma. Nonetheless, its translation to solid tumors faces challenges due to manufacturing complexities, short-lived in vivo persistence, and transient therapeutic impact. We introduce 'Drydux' - an innovative macroporous biomaterial scaffold designed for rapid, efficient in-situ generation of tumor-specific CAR T cells. Drydux expedites CAR T cell preparation with a mere three-day turnaround from patient blood collection, presenting a cost-effective, streamlined alternative to conventional methodologies. Notably, Drydux-enabled CAR T cells provide prolonged in vivo release, functionality, and enhanced persistence exceeding 150 days, with cells transitioning to memory phenotypes. Unlike conventional CAR T cell therapy, which offered only temporary tumor control, equivalent Drydux cell doses induced lasting tumor remission in various animal tumor models, including systemic lymphoma, peritoneal ovarian cancer, metastatic lung cancer, and orthotopic pancreatic cancer. Drydux's approach holds promise in revolutionizing solid tumor CAR T cell therapy by delivering durable, rapid, and cost-effective treatments and broadening patient accessibility to this groundbreaking therapy.

摘要

嵌合抗原受体 (CAR) T 细胞疗法在白血病和淋巴瘤等血液癌症方面取得了革命性的成功。然而,由于制造复杂性、体内存续时间短和治疗效果短暂,其向实体瘤的转化面临挑战。我们引入了“Drydux”——一种用于快速、高效原位生成肿瘤特异性 CAR T 细胞的创新大孔生物材料支架。Drydux 通过从患者血液采集到制备 CAR T 细胞仅需三天的周转时间,加速了 CAR T 细胞的制备过程,与传统方法相比具有成本效益和简化的优势。值得注意的是,Drydux 能够使 CAR T 细胞在体内持续释放、功能和持久性超过 150 天,并使细胞向记忆表型转变。与传统的 CAR T 细胞疗法仅提供暂时的肿瘤控制不同,等效剂量的 Drydux 细胞在各种动物肿瘤模型中诱导了持久的肿瘤缓解,包括系统性淋巴瘤、腹膜卵巢癌、转移性肺癌和原位胰腺癌。Drydux 的方法通过提供持久、快速和经济有效的治疗方法,并扩大患者对这种开创性治疗方法的可及性,有望彻底改变实体瘤 CAR T 细胞治疗。

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