Anže Smole (Avtor), Alexander Benton (Avtor), Mathilde A. Poussin (Avtor), Monika A. Eiva (Avtor), Claudia Mezzanotte (Avtor)

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.

Ključne besede

celice CAR-T;celična imunoterapija;rak;gensko spremenjene imunske celice;urejanje genoma;onkologija;citologija;genomika;CAR-T cells;TCR;inducible;transcription factor;NFAT;single lentiviral expression system;IL-6;IL-12;CRS;armored;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: NIB - Nacionalni inštitut za biologijo
UDK: 616-006
COBISS: 134077187 Povezava se bo odprla v novem oknu
ISSN: 1535-6108
Št. ogledov: 27
Št. prenosov: 6
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: celice CAR-T;celična imunoterapija;rak;gensko spremenjene imunske celice;urejanje genoma;onkologija;citologija;genomika;
Komentar vira: 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.;
Strani: str. 1470-1487, e1-e7
Letnik: ǂVol. ǂ40
Zvezek: ǂiss. ǂ12
Čas izdaje: Dec. 2022
DOI: 10.1016/j.ccell.2022.11.006
ID: 24549622