HLA-C matching status does not affect rituximab-mediated antibody-dependent cellular cytotoxicity by allogeneic natural killer Cells.
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.
Department of Hematology, University of Tsukuba, Tsukuba, Japan.
Takayuki
T
Machino
Yasushi
Y
Okoshi
Yasuyuki
Y
Miyake
Yoshiki
Y
Akatsuka
Shigeru
S
Chiba
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D016219:Immunotherapy, Adoptive; D007519:Isoantigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008212:Lymphocyte Depletion; D008223:Lymphoma / Q000188:drug therapy / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics; D020239:Receptor Cross-Talk; D054340:Receptors, KIR / Q000378:metabolism; D000069283:Rituximab; D014184:Transplantation, Homologous
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D015236:HLA-C Antigens; D007519:Isoantigens; D034741:RNA, Small Interfering; D054340:Receptors, KIR; D000069283:Rituximab