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Berrien-Elliott, Melissa M; Foltz, Jennifer A; Russler-Germain, David A; Neal, Carly C; Tran, Jennifer; Gang, Margery; Wong, Pamela; Fisk, Bryan; Cubitt, Celia C; Marin, Nancy D; Zhou, Alice Y; Jacobs, Miriam T; Foster, Mark; Schappe, Timothy; McClain, Ethan; Kersting-Schadek, Samantha; Desai, Sweta; Pence, Patrick; Becker-Hapak, Michelle; Eisele, Jeremy; Mosior, Matthew; Marsala, Lynne; Griffith, Obi L; Griffith, Malachi; Khan, Saad M; Spencer, David H; DiPersio, John F; Romee, Rizwan; Uy, Geoffrey L; Abboud, Camille N; Ghobadi, Armin; Westervelt, Peter; Stockerl-Goldstein, Keith; Schroeder, Mark A; Wan, Fei; Lie, Wen-Rong; Soon-Shiong, Patrick; Petti, Allegra A; Cashen, Amanda F; Fehniger, Todd A
Science translational medicine, 02/2022, Letnik: 14, Številka: 633Journal Article
Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memory-like (ML) differentiation, whereby NK cells acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, and IL-18. Here, reduced-intensity conditioning (RIC) for -haploidentical hematopoietic cell transplantation (HCT) was augmented with same-donor ML NK cells on day +7 and 3 weeks of N-803 (IL-15 superagonist) to treat patients with relapsed/refractory acute myeloid leukemia (AML) in a clinical trial (NCT02782546). In 15 patients, donor ML NK cells were well tolerated, and 87% of patients achieved a composite complete response at day +28, which corresponded with clearing high-risk mutations, including variants. NK cells were the major blood lymphocytes for 2 months after HCT with 1104-fold expansion (over 1 to 2 weeks). Phenotypic and transcriptional analyses identified donor ML NK cells as distinct from conventional NK cells and showed that ML NK cells persisted for over 2 months. ML NK cells expressed CD16, CD57, and high granzyme B and perforin, along with a unique transcription factor profile. ML NK cells differentiated in patients had enhanced ex vivo function compared to conventional NK cells from both patients and healthy donors. Overall, same-donor ML NK cell therapy with 3 weeks of N-803 support safely augmented RIC haplo-HCT for AML.
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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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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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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