Use of natural killer cells as immunotherapy for leukaemia

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29 Scopus citations

Abstract

Natural killer (NK) cells potentially play a significant role in eradicating residual disease following allogeneic haematopoietic cell transplantation, and have been explored as tools for adoptive immunotherapy for chemotherapy-refractory patients. NK cell cytotoxicity is modulated by multiple activating and inhibitory receptors that maintain a balance between self-tolerance and providing surveillance against pathogens and malignant transformation. The functional characteristics of NK cells are dictated by the strength of inhibitory receptor signalling. Major histocompatibility complex (MHC)-specific inhibitory receptor acquisition occurs sequentially during NK cell development, and is determined by the nature of immunological reconstitution after allogeneic haematopoietic cell transplantation. Polymorphisms of inhibitory receptors [killer immunoglobulin-like receptors (KIRs)] and their ligands (MHC) contribute to interindividual variability. As a result, the functional NK cell repertoire of individual donors has variable potential for graft-vs-leukaemia reactions. Models predicting NK cell alloreactivity, including KIR ligand mismatch and missing KIR ligand strategies, are discussed as algorithms for optimal NK cell donor selection. Future modifications to improve NK cell adoptive immunotherapy by means of increasing target recognition and reducing inhibitory signalling are being explored.

Original languageEnglish (US)
Pages (from-to)467-483
Number of pages17
JournalBest Practice and Research: Clinical Haematology
Volume21
Issue number3
DOIs
StatePublished - Sep 2008

Bibliographical note

Funding Information:
This work was funded by the Children's Cancer Research Fund, Leukemia Research Fund, P01 CA111412 and P01 CA65493.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • NK cells
  • adoptive therapy
  • allogeneic hematopoietic cell transplant
  • graft-vs-leukaemia reaction
  • immunotherapy
  • killer immunoglobulin-like receptors

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