20.500.12556/DiRROS-19389 Expression of inducible factors reprograms CAR-T cells for enhanced function and safety 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. CAR-T cells TCR inducible transcription factor NFAT single lentiviral expression system IL-6 IL-12 CRS armored celice CAR-T celična imunoterapija rak gensko spremenjene imunske celice urejanje genoma onkologija citologija genomika true false false Angleški jezik Slovenski jezik Neznano 2024-07-17 03:56:25 2024-07-18 10:42:09 2024-07-19 03:38:39 0000-00-00 00:00:00 2022 0 0 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.; str. 1470-1487, e1-e7 iss. 12 Vol. 40 Dec. 2022 0000-00-00 PreprintDelovna Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-12-12 616-006 1535-6108 10.1016/j.ccell.2022.11.006 134077187 https://doi.org/10.1016/j.ccell.2022.11.006 1 025c539c-43cf-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26753 Nacionalni inštitut za biologijo 0 0 0