Table I.

Reversal of inhibitory self-recognition (RISER) enhances rituximab-promoted ADCCa

Reagent DonorPercentage of Lysis of EBV-Transformed B Cells by Autologous NK Cells
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No Ab1 ± 0.20.2 ± 0.11.2 ± 0.23.4 ± 1.73.2 ± 2.2
Pan anti-MHC I Ab (DX17)0.4 ± 0.10.5 ± 0.110.6 ± 0.15.9 ± 2.711.5 ± 0.1
RISER combinationb1.3 ± 0.10 ± 0.18.2 ± 0.32.7 ± 0.513.2 ± 0.8
Rituximab6.4 ± 0.114.9 ± 1.550.9 ± 3.425.8 ± 5.879.1 ± 1.5
Rituximab + CD564 ± 0.814.5 ± 0.543.4 ± 1.427.5 ± 5.581.5 ± 1.6
Rituximab + NKG2A (Z199)11.6 ± 0.630.3 ± 0.658.8 ± 3.941.6 ± 0.392.6 ± 1.5
Rituximab + CD94 (HP3B1)9.6 ± 0.620.2 ± 1.353.3 ± 4.429.3 ± 0.588.9 ± 1.8
Rituximab + KIR3DL1 (DX9)6 ± 0.8522 ± 0.355.8 ± 3.020.1 ± 2.181.2 ± 4.5
Rituximab + KIR2DL1 (HP3E4)21.2 ± 013.2 ± 1.351.5 ± 1.129.6 ± 5.278.7 ± 7.5
Rituximab + KIR3DL1, 3DL2, 2DS4 (5.133)4.4 ± 0.315.5 ± 0.947.3 ± 0.829.2 ± 1.973.2 ± 0.7
Rituximab + KIR2DL3, 2DL2, 2DS2 (GL183)6 ± 0.613.1 ± 0.659.8 ± 1.241.1 ± 0.181.9 ± 1.8
Rituximab + Pan anti MHC I antibody (DX17)24.4 ± 0.815.3 ± 0.360.3 ± 2.225.2 ± 4.482.2 ± 1.7
Rituximab + RISER combination*31.2 ± 0.243.4 ± 1.476.3 ± 1.653.4 ± 3.996.9 ± 1.4
  • a NK cells were freshly purified from healthy donors whole blood samples (effector cells). EBV-transformed B cells were labeled with 51Cr (target cells). Cells were incubated at effector to target cells ratio of 10:1 in the presence of Ab combination as specified. All Abs were used at 1 μg/ml concentration. Cytotoxicity was calculated using a 4 h 51Cr -release assay. Results shown are representative of at least three independent experiments.

  • b RISER combination, a combination of NK cell receptor antibodies (Z199, HP3B1, DX9, HP3E4, 5.133, GL183, 1 μ g/ml each).