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Implantable CAR T cell factories enhance solid tumor treatment.

Authors :
Pandit, Sharda
Agarwalla, Pritha
Song, Feifei
Jansson, Anton
Dotti, Gianpietro
Brudno, Yevgeny
Source :
Biomaterials. Jul2024, Vol. 308, pN.PAG-N.PAG. 1p.
Publication Year :
2024

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. Schematics showing conventional CAR T cell manufacturing requiring ∼2 weeks (A) compared to simplified and rapid Drydux mediated in vivo CAR T cell manufacturing (B). [Display omitted] Implantable CAR T cell factories enhance CAR T cell therapy and drastically improve their function and persistence, offering a more effective and accessible cancer treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01429612
Volume :
308
Database :
Academic Search Index
Journal :
Biomaterials
Publication Type :
Academic Journal
Accession number :
176899981
Full Text :
https://doi.org/10.1016/j.biomaterials.2024.122580