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 (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.
Ruggeri
Loredana
L
Division of Haematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, 06122 Perugia, Italy.
Mancusi
Antonella
A
Capanni
Marusca
M
Martelli
Massimo F
MF
Velardi
Andrea
A
D000818:Animals; D016026:Bone Marrow Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D007518:Isoantibodies / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
D007518:Isoantibodies; D007519:Isoantigens