BACKGROUND. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell–based therapy is a promising modality to treat post-HCT relapse. METHODS. We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion. RESULTS. In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires. CONCLUSION. Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.

Shapiro, R., Birch, G., Hu, G., Cadavid, J., Nikiforow, S., Baginska, J., et al. (2022). Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse. THE JOURNAL OF CLINICAL INVESTIGATION, 132(11) [10.1172/JCI154334].

Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse

Rambaldi B.;
2022

Abstract

BACKGROUND. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell–based therapy is a promising modality to treat post-HCT relapse. METHODS. We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion. RESULTS. In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires. CONCLUSION. Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.
Articolo in rivista - Articolo scientifico
Hematopoietic Stem Cell Transplantation; Humans; Interleukin-2; Killer Cells, Natural; Recurrence; Transplantation, Homologous
English
29-mar-2022
2022
132
11
e154334
open
Shapiro, R., Birch, G., Hu, G., Cadavid, J., Nikiforow, S., Baginska, J., et al. (2022). Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse. THE JOURNAL OF CLINICAL INVESTIGATION, 132(11) [10.1172/JCI154334].
File in questo prodotto:
File Dimensione Formato  
Shapiro-2022-Journal of Clinical Investigation-VoR.pdf

accesso aperto

Descrizione: . This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 4.2 MB
Formato Adobe PDF
4.2 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/524264
Citazioni
  • Scopus 73
  • ???jsp.display-item.citation.isi??? 70
Social impact