Implantable CAR T cell factories enhance solid tumor treatment

嵌合抗原受体 癌症研究 淋巴瘤 体内 医学 癌症 卵巢癌 免疫疗法 免疫学 内科学 生物 生物技术
作者
Sharda Pandit,Pritha Agarwalla,Feifei Song,Anton Jansson,Gianpietro Dotti,Yevgeny Brudno
出处
期刊:Biomaterials [Elsevier]
卷期号:308: 122580-122580 被引量:10
标识
DOI:10.1016/j.biomaterials.2024.122580
摘要

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.

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