Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma.
In: Angewandte Chemie International Edition, Jg. 62 (2023-10-26), Heft 44, S. 1-8
Online
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Zugriff:
Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B‐cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild‐type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre‐clinical potential to treat hematological malignancies. [ABSTRACT FROM AUTHOR]
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Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma.
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Autor/in / Beteiligte Person: | Álvarez‐Benedicto, Ester ; Tian, Zeru ; Chatterjee, Sumanta ; Orlando, Domenico ; Kim, Minjeong ; Guerrero, Erick D. ; Wang, Xu ; Siegwart, Daniel J. |
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Zeitschrift: | Angewandte Chemie International Edition, Jg. 62 (2023-10-26), Heft 44, S. 1-8 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 1433-7851 (print) |
DOI: | 10.1002/anie.202310395 |
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