2022
DOI: 10.1126/scitranslmed.abm1375
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Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia

Abstract: 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-int… Show more

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Cited by 65 publications
(61 citation statements)
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“…Very recently, in AML patients receiving haploidentical HCT, infused CIML NK cells derived from the same donor persisted for a long time and were highly functional. More importantly, 87% of patients achieved a composite complete response ( 71 ). Another recent report described the therapeutic effect of CIML NK cell infusion to patients with relapsed myeloid diseases after haploidentical HCT.…”
Section: Cytokine-induced Memory-like (Ciml) Nk Cellsmentioning
confidence: 99%
“…Very recently, in AML patients receiving haploidentical HCT, infused CIML NK cells derived from the same donor persisted for a long time and were highly functional. More importantly, 87% of patients achieved a composite complete response ( 71 ). Another recent report described the therapeutic effect of CIML NK cell infusion to patients with relapsed myeloid diseases after haploidentical HCT.…”
Section: Cytokine-induced Memory-like (Ciml) Nk Cellsmentioning
confidence: 99%
“…These acquired advantages have been reproduced in different preclinical studies and phase I/II clinical trials demonstrating a suitable safety profile and promising efficacy, achieving 56% OR rate and 44% CR rate in AML and MDS patients (NCT01898793). CIML-NK clinical trials are also ongoing in a haploidentical hematopoietic cell transplantation (HCT) context (NCT02782546) ( 107 ) or donor-derived adoptive therapy in post-HCT AML relapse setting (NCT04024761, NCT03068819) ( 108 , 109 ). Moreover, CIML-NK combinatorial approaches with chemotherapy (e.g.…”
Section: Manufacturing Conditions: Key Aspect For the Efficacy Of Car...mentioning
confidence: 99%
“…Moreover, CIML-NK combinatorial approaches with chemotherapy (e.g. Ara-C), IL-15 superagonist (NCT02782546) ( 107 ), NK-cell engagers (NCT04074746) ( 110 ), or a CD38-antibody recruiting molecule (NCT04634435) ( 111 ) are also being developed. Regarding CAR-NK context, CIML-NK modified to express CD19 CAR exhibited synergism on CAR activation and demonstrated the aforementioned CIML-NK advantages in an NK-resistant lymphoma model ( 112 ).…”
Section: Manufacturing Conditions: Key Aspect For the Efficacy Of Car...mentioning
confidence: 99%
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“…These include adoptive transfer of cytokine-induced memory-like NK cells or chimeric antigen receptor NK (CAR-NK) cells. Currently, numerous clinical trials using such approaches are ongoing, but the efficacy of these treatments still needs to be evaluated ( 5 , 6 ). In this context, understanding the complex processes employed by tumor cells to evade NK-cell immunity is crucial.…”
Section: Introductionmentioning
confidence: 99%