Antibody-dependent cell cytotoxicity to breast cancer targets despite inhibitory KIR signaling.
BACKGROUND
Natural killer (NK) cells express killer immunoglobulin-like (KIR) inhibitory receptors, which recognize certain HLA class I molecules (KIR ligands), and stimulatory receptors such as FcgammaRIII. The purpose of this study was to test the possible influence of inhibitory KIR signaling on antibody-dependent cell cytotoxicity (ADCC) mediated by allogeneic NK cells against breast cancer targets.


METHODS
The cytotoxic activity of volunteer donor NK cells against the cell lines SKBR-3, T47D and MCF-7, which have high, low and no HER2 gene amplification, respectively, were studied. Both cell lines and donors were assigned to the C1 or C2 superfamily, defined by the structure of the HLA-Cw molecule.


RESULTS
It was found that ADCC mediated by allogeneic NK cells occurred despite combinations of NK cells and breast cancer targets predicted to trigger inhibitory KIR signaling.


CONCLUSIONS
We suggest that adoptive immunotherapy with allogeneic NK cells and trastuzumab may be an effective combination against breast cancer targets.
Stein
Mark N
MN
Mount Sinai School of Medicine, New York, NY 10029, USA.
Shin
James
J
Gudzowaty
Oksana
O
Bernstein
Andrew M
AM
Liu
Johnson M
JM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D005784:Gene Amplification; D015236:HLA-C Antigens / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D020559:Monomeric GTP-Binding Proteins / Q000276:immunology*; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015236:HLA-C Antigens; D020559:Monomeric GTP-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C490245:GEM protein, human