Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387233417> ?p ?o ?g. }
- W4387233417 abstract "Abstract Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. We investigated the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using a validated in vitro model for exhaustion, RNA and ATAC sequencing on baseline and chronically stimulated CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identified IL-4 as a key regulator of CART cell dysfunction. Further, when CART cells were treated with IL-4, they developed signs of exhaustion, but when CART cells were treated with an IL-4 monoclonal antibody, they showed improved antitumor efficacy and reduced signs of exhaustion in preclinical models. Therefore, our study identified both a novel role for IL-4 on CART cells and the improvement of CART cell therapy through IL-4 neutralization. Statement of Significance Identifying regulators of CART cell exhaustion will not only enhance the field’s understanding of therapeutic failure, but it will also provide avenues to enhance CART cell efficacy. This study reveals both a novel role for IL-4 in exhaustion and a strategy to improve CART cell activity through IL-4 neutralization." @default.
- W4387233417 created "2023-10-02" @default.
- W4387233417 creator A5000383195 @default.
- W4387233417 creator A5003521951 @default.
- W4387233417 creator A5008200184 @default.
- W4387233417 creator A5012147403 @default.
- W4387233417 creator A5015801018 @default.
- W4387233417 creator A5020001580 @default.
- W4387233417 creator A5021207672 @default.
- W4387233417 creator A5025066483 @default.
- W4387233417 creator A5045538190 @default.
- W4387233417 creator A5048214136 @default.
- W4387233417 creator A5051172989 @default.
- W4387233417 creator A5052209523 @default.
- W4387233417 creator A5052820999 @default.
- W4387233417 creator A5054196868 @default.
- W4387233417 creator A5057231484 @default.
- W4387233417 creator A5062638192 @default.
- W4387233417 creator A5069450479 @default.
- W4387233417 creator A5072015517 @default.
- W4387233417 creator A5077073941 @default.
- W4387233417 creator A5083661436 @default.
- W4387233417 creator A5090781979 @default.
- W4387233417 date "2023-09-30" @default.
- W4387233417 modified "2023-10-16" @default.
- W4387233417 title "The Identification of IL-4 as a Regulator of Chimeric Antigen Receptor T Cell Exhaustion" @default.
- W4387233417 cites W1533188705 @default.
- W4387233417 cites W1619537825 @default.
- W4387233417 cites W1987337968 @default.
- W4387233417 cites W1995908153 @default.
- W4387233417 cites W2001042507 @default.
- W4387233417 cites W2031211461 @default.
- W4387233417 cites W2058031589 @default.
- W4387233417 cites W2067468716 @default.
- W4387233417 cites W2149554811 @default.
- W4387233417 cites W2201689894 @default.
- W4387233417 cites W2480571942 @default.
- W4387233417 cites W2597268880 @default.
- W4387233417 cites W2737193923 @default.
- W4387233417 cites W2773804840 @default.
- W4387233417 cites W2903062212 @default.
- W4387233417 cites W2903225254 @default.
- W4387233417 cites W2903754922 @default.
- W4387233417 cites W2917101705 @default.
- W4387233417 cites W2917547201 @default.
- W4387233417 cites W2919051790 @default.
- W4387233417 cites W2947617159 @default.
- W4387233417 cites W2958308511 @default.
- W4387233417 cites W2973860127 @default.
- W4387233417 cites W2979874482 @default.
- W4387233417 cites W2992056665 @default.
- W4387233417 cites W2992738455 @default.
- W4387233417 cites W3005578003 @default.
- W4387233417 cites W3020888809 @default.
- W4387233417 cites W3119561596 @default.
- W4387233417 cites W3135234497 @default.
- W4387233417 cites W3150736119 @default.
- W4387233417 cites W3163223830 @default.
- W4387233417 cites W3163599487 @default.
- W4387233417 cites W3183788950 @default.
- W4387233417 cites W3213155546 @default.
- W4387233417 cites W3216414181 @default.
- W4387233417 cites W3216793704 @default.
- W4387233417 cites W4221078021 @default.
- W4387233417 cites W4221128181 @default.
- W4387233417 cites W4224219068 @default.
- W4387233417 cites W4283328628 @default.
- W4387233417 cites W4295203267 @default.
- W4387233417 cites W4297380470 @default.
- W4387233417 cites W4306155265 @default.
- W4387233417 cites W4308654310 @default.
- W4387233417 cites W4321607142 @default.
- W4387233417 cites W4324309777 @default.
- W4387233417 cites W4327714584 @default.
- W4387233417 cites W4362507505 @default.
- W4387233417 doi "https://doi.org/10.1101/2023.09.28.560046" @default.
- W4387233417 hasPublicationYear "2023" @default.
- W4387233417 type Work @default.
- W4387233417 citedByCount "0" @default.
- W4387233417 crossrefType "posted-content" @default.
- W4387233417 hasAuthorship W4387233417A5000383195 @default.
- W4387233417 hasAuthorship W4387233417A5003521951 @default.
- W4387233417 hasAuthorship W4387233417A5008200184 @default.
- W4387233417 hasAuthorship W4387233417A5012147403 @default.
- W4387233417 hasAuthorship W4387233417A5015801018 @default.
- W4387233417 hasAuthorship W4387233417A5020001580 @default.
- W4387233417 hasAuthorship W4387233417A5021207672 @default.
- W4387233417 hasAuthorship W4387233417A5025066483 @default.
- W4387233417 hasAuthorship W4387233417A5045538190 @default.
- W4387233417 hasAuthorship W4387233417A5048214136 @default.
- W4387233417 hasAuthorship W4387233417A5051172989 @default.
- W4387233417 hasAuthorship W4387233417A5052209523 @default.
- W4387233417 hasAuthorship W4387233417A5052820999 @default.
- W4387233417 hasAuthorship W4387233417A5054196868 @default.
- W4387233417 hasAuthorship W4387233417A5057231484 @default.
- W4387233417 hasAuthorship W4387233417A5062638192 @default.
- W4387233417 hasAuthorship W4387233417A5069450479 @default.
- W4387233417 hasAuthorship W4387233417A5072015517 @default.
- W4387233417 hasAuthorship W4387233417A5077073941 @default.
- W4387233417 hasAuthorship W4387233417A5083661436 @default.