| Naslov: | Expression of inducible factors reprograms CAR-T cells for enhanced function and safety |
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| Avtorji: | ID Smole, Anže (Avtor)
ID Benton, Alexander (Avtor)
ID Poussin, Mathilde A. (Avtor)
ID Eiva, Monika A. (Avtor)
ID Mezzanotte, Claudia (Avtor) |
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| Datoteke: |  URL - Izvorni URL, za dostop obiščite https://doi.org/10.1016/j.ccell.2022.11.006
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| Jezik: | Angleški jezik |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: |  NIB - Nacionalni inštitut za biologijo
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| Povzetek: | 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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| Ključne besede: | CAR-T cells, TCR, inducible, transcription factor, NFAT, single lentiviral expression system, IL-6, IL-12, CRS, armored |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Preprint, delovna različica publikacije (nerecenzirana) |
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| Datum objave: | 12.12.2022 |
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| Leto izida: | 2022 |
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| Št. strani: | str. 1470-1487, e1-e7 |
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| Številčenje: | Vol. 40, iss. 12 |
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| PID: | 20.500.12556/DiRROS-19389  |
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| UDK: | 616-006 |
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| ISSN pri članku: | 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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| Opomba: | 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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| Datum objave v DiRROS: | 18.07.2024 |
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| Število ogledov: | 368 |
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| Število prenosov: | 72 |
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| Metapodatki: |    |
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