Exploitation of alloreactive NK cells in adoptive immunotherapy of cancer

NK cells are primed to kill by several activating receptors. Killing of autologous cells is prevented as NK cells co-express inhibitory receptors for self-MHC class I molecules. Human NK cells discriminate between different allelic forms of MHC molecules via killer cell immunoglobulin-like receptors...

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Bibliographic Details
Published in:Current opinion in immunology 2005-04, Vol.17 (2), p.211-217
Main Authors: Ruggeri, Loredana, Mancusi, Antonella, Capanni, Marusca, Martelli, Massimo F, Velardi, Andrea
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Transplantation
Humans
Immunotherapy, Adoptive
Isoantibodies - immunology
Isoantigens - immunology
Killer Cells, Natural - immunology
Neoplasms - immunology
Neoplasms - therapy
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Summary:NK cells are primed to kill by several activating receptors. Killing of autologous cells is prevented as NK cells co-express inhibitory receptors for self-MHC class I molecules. Human NK cells discriminate between different allelic forms of MHC molecules via killer cell immunoglobulin-like receptors (KIRs), which are clonally distributed, and each cell in the repertoire bears at least one receptor that is specific for self-MHC class I molecules. Consequently, when faced with mismatched allogeneic targets, NK cells in the repertoire will sense the missing expression of self-MHC class I alleles and will mediate alloreactions. Recent studies in murine transplant models and data from mismatched haematopoietic transplant trials demonstrate MHC class I mismatches, which generate an alloreactive NK-cell response in the graft-versus-host direction, eradicate leukaemia, improve engraftment and protect against T-cell-mediated graft-versus-host disease.
ISSN:0952-7915
1879-0372
DOI:10.1016/j.coi.2005.01.007