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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
12345
No Ab 1 ± 0.2 0.2 ± 0.1 1.2 ± 0.2 3.4 ± 1.7 3.2 ± 2.2 
Pan anti-MHC I Ab (DX17) 0.4 ± 0.1 0.5 ± 0.1 10.6 ± 0.1 5.9 ± 2.7 11.5 ± 0.1 
RISER combinationb 1.3 ± 0.1 0 ± 0.1 8.2 ± 0.3 2.7 ± 0.5 13.2 ± 0.8 
Rituximab 6.4 ± 0.1 14.9 ± 1.5 50.9 ± 3.4 25.8 ± 5.8 79.1 ± 1.5 
Rituximab + CD56 4 ± 0.8 14.5 ± 0.5 43.4 ± 1.4 27.5 ± 5.5 81.5 ± 1.6 
Rituximab + NKG2A (Z199) 11.6 ± 0.6 30.3 ± 0.6 58.8 ± 3.9 41.6 ± 0.3 92.6 ± 1.5 
Rituximab + CD94 (HP3B1) 9.6 ± 0.6 20.2 ± 1.3 53.3 ± 4.4 29.3 ± 0.5 88.9 ± 1.8 
Rituximab + KIR3DL1 (DX9) 6 ± 0.85 22 ± 0.3 55.8 ± 3.0 20.1 ± 2.1 81.2 ± 4.5 
Rituximab + KIR2DL1 (HP3E4) 21.2 ± 0 13.2 ± 1.3 51.5 ± 1.1 29.6 ± 5.2 78.7 ± 7.5 
Rituximab + KIR3DL1, 3DL2, 2DS4 (5.133) 4.4 ± 0.3 15.5 ± 0.9 47.3 ± 0.8 29.2 ± 1.9 73.2 ± 0.7 
Rituximab + KIR2DL3, 2DL2, 2DS2 (GL183) 6 ± 0.6 13.1 ± 0.6 59.8 ± 1.2 41.1 ± 0.1 81.9 ± 1.8 
Rituximab + Pan anti MHC I antibody (DX17) 24.4 ± 0.8 15.3 ± 0.3 60.3 ± 2.2 25.2 ± 4.4 82.2 ± 1.7 
Rituximab + RISER combination* 31.2 ± 0.2 43.4 ± 1.4 76.3 ± 1.6 53.4 ± 3.9 96.9 ± 1.4 
Reagent DonorPercentage of Lysis of EBV-Transformed B Cells by Autologous NK Cells
12345
No Ab 1 ± 0.2 0.2 ± 0.1 1.2 ± 0.2 3.4 ± 1.7 3.2 ± 2.2 
Pan anti-MHC I Ab (DX17) 0.4 ± 0.1 0.5 ± 0.1 10.6 ± 0.1 5.9 ± 2.7 11.5 ± 0.1 
RISER combinationb 1.3 ± 0.1 0 ± 0.1 8.2 ± 0.3 2.7 ± 0.5 13.2 ± 0.8 
Rituximab 6.4 ± 0.1 14.9 ± 1.5 50.9 ± 3.4 25.8 ± 5.8 79.1 ± 1.5 
Rituximab + CD56 4 ± 0.8 14.5 ± 0.5 43.4 ± 1.4 27.5 ± 5.5 81.5 ± 1.6 
Rituximab + NKG2A (Z199) 11.6 ± 0.6 30.3 ± 0.6 58.8 ± 3.9 41.6 ± 0.3 92.6 ± 1.5 
Rituximab + CD94 (HP3B1) 9.6 ± 0.6 20.2 ± 1.3 53.3 ± 4.4 29.3 ± 0.5 88.9 ± 1.8 
Rituximab + KIR3DL1 (DX9) 6 ± 0.85 22 ± 0.3 55.8 ± 3.0 20.1 ± 2.1 81.2 ± 4.5 
Rituximab + KIR2DL1 (HP3E4) 21.2 ± 0 13.2 ± 1.3 51.5 ± 1.1 29.6 ± 5.2 78.7 ± 7.5 
Rituximab + KIR3DL1, 3DL2, 2DS4 (5.133) 4.4 ± 0.3 15.5 ± 0.9 47.3 ± 0.8 29.2 ± 1.9 73.2 ± 0.7 
Rituximab + KIR2DL3, 2DL2, 2DS2 (GL183) 6 ± 0.6 13.1 ± 0.6 59.8 ± 1.2 41.1 ± 0.1 81.9 ± 1.8 
Rituximab + Pan anti MHC I antibody (DX17) 24.4 ± 0.8 15.3 ± 0.3 60.3 ± 2.2 25.2 ± 4.4 82.2 ± 1.7 
Rituximab + RISER combination* 31.2 ± 0.2 43.4 ± 1.4 76.3 ± 1.6 53.4 ± 3.9 96.9 ± 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).

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