| Title: | Expression of inducible factors reprograms CAR-T cells for enhanced function and safety |
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| Authors: | ID Smole, Anže (Author)
ID Benton, Alexander (Author)
ID Poussin, Mathilde A. (Author)
ID Eiva, Monika A. (Author)
ID Mezzanotte, Claudia (Author) |
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| Files: |  URL - Source URL, visit https://doi.org/10.1016/j.ccell.2022.11.006
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | Despite the success of CAR-T cell cancer immunotherapy, challenges in efficacy and safety remain. Investigators have begun to enhance CAR-T cells with the expression of accessory molecules to address these challenges. Current systems rely on constitutive transgene expression or multiple viral vectors, resulting in unregulated response and product heterogeneity. Here, we develop a genetic platform that combines autonomous antigen-induced production of an accessory molecule with constitutive CAR expression in a single lentiviral vector called Uni-Vect. The broad therapeutic application of Uni-Vect is demonstrated in vivo by activation-dependent expression of (1) an immunostimulatory cytokine that improves efficacy, (2) an antibody that ameliorates cytokine-release syndrome, and (3) transcription factors that modulate T cell biology. Uni-Vect is also implemented as a platform to characterize immune receptors. Overall, we demonstrate that Uni-Vect provides a foundation for a more clinically actionable next-generation cellular immunotherapy. |
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| Keywords: | CAR-T cells, TCR, inducible, transcription factor, NFAT, single lentiviral expression system, IL-6, IL-12, CRS, armored |
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| Publication status: | Published |
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| Publication version: | Preprint, working version of publication, not peer-reviewed |
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| Publication date: | 12.12.2022 |
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| Year of publishing: | 2022 |
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| Number of pages: | str. 1470-1487, e1-e7 |
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| Numbering: | Vol. 40, iss. 12 |
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| PID: | 20.500.12556/DiRROS-19389  |
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| UDC: | 616-006 |
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| ISSN on article: | 1535-6108 |
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| DOI: | 10.1016/j.ccell.2022.11.006 |
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| COBISS.SI-ID: | 134077187 |
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| Note: | Ostali avtorji: Alexander Benton, Mathilde A. Poussin, Monika A. Eiva, Claudia Mezzanotte, Barbara Camisa, Beatrice Greco, Prannda Sharma, Nicholas G. Minutolo, Falon Gray, Adham S. Bear, Miren L. Baroja, Casey Cummins, Chong Xu, Francesca Sanvito, Andrea Lang Goldgewicht, Tatiana Blanchard, Alba Rodriguez-Garcia, Michael Klichinsky, Chiara Bonini, Carl H. June, Avery D. Posey Jr., Gerald P. Linette, Beatriz M. Carreno, Monica Casucci, Daniel J. Powell Jr.;
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| Publication date in DiRROS: | 18.07.2024 |
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| Views: | 367 |
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| Downloads: | 72 |
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