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Meyran, Deborah; Zhu, Joe Jiang; Butler, Jeanne; Tantalo, Daniela; MacDonald, Sean; Nguyen, Thu Ngoc; Wang, Minyu; Thio, Niko; D'Souza, Criselle; Qin, Vicky Mengfei; Slaney, Clare; Harrison, Aaron; Sek, Kevin; Petrone, Pasquale; Thia, Kevin; Giuffrida, Lauren; Scott, Andrew M; Terry, Rachael L; Tran, Ben; Desai, Jayesh; Prince, H Miles; Harrison, Simon J; Beavis, Paul A; Kershaw, Michael H; Solomon, Ben; Ekert, Paul G; Trapani, Joseph A; Darcy, Phillip K; Neeson, Paul J
Science translational medicine, 04/2023, Letnik: 15, Številka: 690Journal Article
Patients who receive chimeric antigen receptor (CAR)-T cells that are enriched in memory T cells exhibit better disease control as a result of increased expansion and persistence of the CAR-T cells. Human memory T cells include stem-like CD8 memory T cell progenitors that can become either functional stem-like T (T ) cells or dysfunctional T progenitor exhausted (T ) cells. To that end, we demonstrated that T cells were less abundant in infused CAR-T cell products in a phase 1 clinical trial testing Lewis Y-CAR-T cells (NCT03851146), and the infused CAR-T cells displayed poor persistence in patients. To address this issue, we developed a production protocol to generate T -like CAR-T cells enriched for expression of genes in cell replication pathways. Compared with conventional CAR-T cells, T -like CAR-T cells had enhanced proliferative capacity and increased cytokine secretion after CAR stimulation, including after chronic CAR stimulation in vitro. These responses were dependent on the presence of CD4 T cells during T -like CAR-T cell production. Adoptive transfer of T -like CAR-T cells induced better control of established tumors and resistance to tumor rechallenge in preclinical models. These more favorable outcomes were associated with increased persistence of T -like CAR-T cells and an increased memory T cell pool. Last, T -like CAR-T cells and anti-programmed cell death protein 1 (PD-1) treatment eradicated established tumors, and this was associated with increased tumor-infiltrating CD8 CAR T cells producing interferon-γ. In conclusion, our CAR-T cell protocol generated T -like CAR-T cells with enhanced therapeutic efficacy, resulting in increased proliferative capacity and persistence in vivo.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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