The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial

Lee, Kyoo-Hyung; Yoon, Suk Ran; Gong, Jeong-Ryeol; Choi, Eun Ji; Kim, Hun Sik; Park, Chan‐Jeoung; Yun, Sung‐Cheol; Park, Soo Yeon; Jung, Sol-Ji; Kim, Hanna; Lee, Soo Yun; Jung, Hye Young; Byun, Jaechul; Kim, Mirang; Kim, Seon‐Young; Kim, Jeong‐Hwan; Lee, Je Hwan; Lee, Jung‐Hee; Choi, Yunsuk; Park, Han‐Seung; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Woo, Ji-Min; Kang, Hyeran; Baek, Seunghyun; Kim, Su Mi; Kim, Hoon-Min; Cho, Kwang-Hyun; Choi, Inpyo

doi:10.1038/s41375-023-01849-5

Cited by 13 publications

(4 citation statements)

References 53 publications

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“…No significant differences in engraftment rate, incidence of GVHD or viral reactivation were demonstrated between study patients and control. In a subgroup of active AML or MDS patients, CR rate post haplo-SCT with NK cell therapy was 77% (23/30) 123 . Other clinical studies also showed safety and efficacy of NK cell therapy after transplantation [124][125][126][127] , including for pediatric solid tumors 128 (Table 2).…”

Section: Comparative Studies Of Natural Killer Cell Therapy After Ste...mentioning

confidence: 99%

Adoptive cellular therapy after hematopoietic stem cell transplantation

Vittayawacharin,

Kongtim,

Chu

et al. 2024

American J Hematol

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Effective cellular therapy using CD19 chimeric antigen receptor T‐cells for the treatment of advanced B‐cell malignancies raises the question of whether the administration of adoptive cellular therapy (ACT) posttransplant could reduce relapse and improve survival. Moreover, several early phase clinical studies have shown the potential beneficial effects of administration of tumor‐associated antigen‐specific T‐cells and natural killer cells posttransplant for high‐risk patients, aiming to decrease relapse and possibly improve survival. In this article, we present an in‐depth review of ACT after transplantation, which has the potential to significantly improve the efficacy of this procedure and revolutionize this field.

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Section: Comparative Studies Of Natural Killer Cell Therapy After Ste...mentioning

confidence: 99%

Adoptive cellular therapy after hematopoietic stem cell transplantation

Vittayawacharin,

Kongtim,

Chu

et al. 2024

American J Hematol

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“… 102 A phase II randomized trial in high-risk AML and MDS patients after haploidentical HCT also demonstrated the benefits of NK-cell therapy after haploidentical HCT in reducing disease progression. 103 Following the successful treatment of lymphoma, several trials have evaluated the role of chimeric CAR (chimeric antigen receptor)-T cells in MDS and other advanced myeloid neoplasms. CAR-T cells need to have a certain degree of specificity for malignant cells to ensure that there are healthy progenitors to repopulate the BM in time to avoid complications.…”

Section: Adoptive Cell Therapymentioning

confidence: 99%

Immune dysregulation and potential targeted therapy in myelodysplastic syndrome

Zhang

Yang

et al. 2023

Therapeutic Advances in Hematology

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Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological diseases and a high risk for transformation to acute myeloid leukemia (AML). The identification of key genetic alterations in MDS has enhanced our understanding of the pathogenesis and evolution. In recent years, it has been found that both innate and adaptive immune signaling are activated in the hematopoietic niche of MDS with aberrant cytokine secretion in the bone marrow microenvironment. It is also clear that immune dysregulation plays an important role in the occurrence and progression of MDS, especially the destruction of the bone marrow microenvironment, including hematopoiesis and stromal components. The purpose of this review is to explore the role of immune cells, the immune microenvironment, and cytokines in the pathogenesis of MDS. Insights into the mechanisms of these variants may facilitate the development of novel effective treatments to prevent disease progression.

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“…A landmark study by Miller et al (13) already showed the feasibility and safety of CD3-depleted, overnight (O/N) IL-2 stimulated cells in AML. After that, NK cells or cell products with different stimulation protocols, mostly IL-2 (14)(15)(16)(17) or a cytokine combination O/N (18,19) have been used in clinical trials, again along with HSCT or without it. Moreover, longer cultures with cytokines (20) or feeder cells have been used in the clinical setting (21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

“…A landmark study by Miller et al (13) already showed the feasibility and safety of CD3-depleted, overnight (O/N) IL-2 stimulated cells in AML. After that, NK cells or cell products with different stimulation protocols, mostly IL-2 (14)(15)(16)(17) or a cytokine combination O/N (18,19) have been used in clinical trials, again along with HSCT or without . CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Introductionmentioning

confidence: 99%

Automated and closed clinical-grade manufacturing protocol produces potent NK cells against neuroblastoma cells and AML blasts

Jahan,

Penna,

Luostarinen

et al. 2024

Preprint

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Natural killer (NK) cells have great potential as allogeneic immune cell therapy due to their natural ability to recognize and kill tumor cells, and due to their apparent safety. This study describes the development of an immunotherapy option tailored for high-risk acute myeloid leukemia (AML) in adults and neuroblastoma in children. A GMP-compliant manufacturing protocol for the local production of functionally potent NK cells is detailed in the study, including a comprehensive description of the quality control strategy and considerations for product batch specifications in early clinical development. The protocol is based on the closed, automated CliniMACS Prodigy® platform (Miltenyi Biotec) and a modified Natural Killer Cell Transduction (NKCT) process without transduction and expansion. NK cells are isolated from leukapheresis through CD3 depletion and CD56 enrichment, followed by a 12-hour activation with cytokines (500 IU/ml IL-2, 140 IU/ml IL-15). Three CliniMACS Prodigy® NKCT processes were executed, demonstrating the feasibility and consistency of the modified NKCT process. A three-step process without expansion, however, compromised the NK cell yield. T cells were depleted effectively, indicating excellent safety of the product for allogeneic use. Phenotypic and functional characterization of the NK cells before and after cytokine activation revealed a notable increase in the expression of activation markers, particularly CD69, consistent with enhanced functionality. Intriguingly, even following a brief 12-hour activation period, the NK cells exhibited increased killing efficacy against CD33+ AML blasts isolated from patients and against SH-SY5Y neuroblastoma (NBL) target cells in vitro, suggesting a potential therapeutic benefit for AML and NBL patients.

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The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial

Cited by 13 publications

References 53 publications

Adoptive cellular therapy after hematopoietic stem cell transplantation

Adoptive cellular therapy after hematopoietic stem cell transplantation

Immune dysregulation and potential targeted therapy in myelodysplastic syndrome

Automated and closed clinical-grade manufacturing protocol produces potent NK cells against neuroblastoma cells and AML blasts

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