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Implantable CAR T cell factories enhance solid tumor treatment
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, United States.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, United States.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jönköping University, School of Engineering, JTH, Product Development, Production and Design, JTH, Product design and development (PDD).ORCID iD: 0000-0002-9362-8328
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2024 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 308, article id 122580Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2024. Vol. 308, article id 122580
Keywords [en]
Biomaterials, CAR T cell, Cell therapy, immunotherapy, implant, porous matrix, Cost effectiveness, Cytology, Diseases, Oncology, Patient treatment, Scaffolds (biology), Tumors, alginic acid, biomaterial, chimeric antigen receptor, drydux, gamma interferon, interleukin 15, interleukin 2, macrophage inflammatory protein 1alpha, Antigen receptors, Chimeric antigen receptor T cell, In-vivo, Manufacturing complexity, Porous matrixs, Solid tumors, Tumor treatment, A-549 cell line, animal experiment, animal model, animal tissue, antineoplastic activity, Article, bioluminescence, chimeric antigen receptor T-cell immunotherapy, computer assisted tomography, controlled study, cytotoxicity, enzyme linked immunosorbent assay, female, flow cytometry, human, human cell, immunofluorescence, lung metastasis, mouse, nonhuman, nuclear reprogramming, ovary cancer, overall survival, PANC-1 cell line, pancreas cancer, peripheral blood mononuclear cell, peritoneum, phenotype, SK-OV-3 cell line, solid tumor, tumor growth, tumor microenvironment, tumor regression, tumor volume, T-cells
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:hj:diva-64087DOI: 10.1016/j.biomaterials.2024.122580ISI: 001291625800001PubMedID: 38640784Scopus ID: 2-s2.0-85190749625Local ID: ;intsam;949383OAI: oai:DiVA.org:hj-64087DiVA, id: diva2:1855407
Available from: 2024-04-30 Created: 2024-04-30 Last updated: 2024-08-26Bibliographically approved

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