RRC ID 75896
Author Machino T, Okoshi Y, Miyake Y, Akatsuka Y, Chiba S.
Title HLA-C matching status does not affect rituximab-mediated antibody-dependent cellular cytotoxicity by allogeneic natural killer Cells.
Journal Immunol Invest
Abstract Risk of leukemia relapse after T cell-depleted hematopoietic stem cell transplantation is lower in the "HLA-C mismatched" recipient-donor combinations. This might be attributable to increased natural killing by allogeneic NK cells carrying a KIR that does not bind to HLA-C on target cells (HLA-C-uncoupled KIR). Considering a new strategy of allogeneic NK cell transfer with rituximab to treat B-cell lymphomas, however, it is unknown whether the HLA-C matching status also affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC). To address this issue, we investigated the levels of ADCC by purified NK cells carrying an HLA-C-uncoupled KIR, where the NK cell donors had either matched or mismatched HLA-C combination with target cells. Purified NK cells carrying an HLA-C-uncoupled KIR consistently showed enhanced ADCC against target cells when NK cell donors had an HLA-C-mismatch. When NK cell donors did not have an HLA-C mismatch, it was inconsistent whether HLA-C-uncoupled KIR caused ADCC enhancement. When the levels of ADCC by whole NK cells were compared, there were substantial differences among the donors regardless of the HLA-C matching status. Subjects with HLA-C mismatch may not have an advantage when cytoimmunotherapy using allogeneic NK cells is considered in combination with rituximab.
Volume 41(8)
Pages 831-46
Published 2012-1-1
DOI 10.3109/08820139.2012.691148
PMID 22676066
MeSH Antibodies, Monoclonal, Murine-Derived / administration & dosage* Antibody-Dependent Cell Cytotoxicity / immunology* Antigens, CD20 / immunology Antineoplastic Agents / administration & dosage* B-Lymphocytes / immunology Cell Line, Tumor Gene Knockdown Techniques HLA-C Antigens / genetics HLA-C Antigens / immunology* Histocompatibility* Humans Immunotherapy, Adoptive* Isoantigens / immunology Killer Cells, Natural / immunology Killer Cells, Natural / transplantation* Lymphocyte Depletion Lymphoma / drug therapy Lymphoma / therapy* RNA, Small Interfering / genetics Receptor Cross-Talk Receptors, KIR / metabolism Rituximab Transplantation, Homologous
IF 2.511
Resource
Human and Animal Cells RAJI(RCB1647)