HLA-C matching status does not affect rituximab-mediated antibody-dependent cellular cytotoxicity by allogeneic natural killer Cells

Immunol Invest. 2012;41(8):831-46. doi: 10.3109/08820139.2012.691148. Epub 2012 Jun 8.

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.

MeSH terms

  • 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

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • HLA-C Antigens
  • Isoantigens
  • RNA, Small Interfering
  • Receptors, KIR
  • Rituximab