|
|
Blood, 15 October 2006, Vol. 108, No. 8, pp. 2648-2654.
Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2006-04-020057.
 Previous Article | Next Article 
Submitted April 28, 2006
Accepted May 8, 2006
Anti-CD20 monoclonal antibody with enhanced affinity for
CD16 activates NK cells at lower concentrations and more
effectively than rituximab
Julie A Bowles, Siao-Yi Wang, Brian K Link, Barrett Allen, Gregory Beuerlein, Mary A Campbell, David Marquis, Brian Ondek, James E Wooldridge, Brian J Smith, James B Breitmeyer, and George J Weiner*
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Applied Molecular Evolution, San Diego, CA, USA
* Corresponding author; email: george-weiner{at}uiowa.edu.
Growing evidence indicates the affinity of mAb for CD16
(Fc RIII) plays a central role in the ability of
the mAb to mediate anti-tumor activity. We evaluated
how CD16 polymorphisms, and mAb with modified affinity
for target antigen and CD16, impact on NK cell phenotype
when CD20 (+) lymphoma cells were also present. MAb
consisted of rituximab (R), anti-CD20 with enhanced
affinity for CD20 (AME-B), and anti-CD20 with enhanced
affinity for both CD20 and CD16 (AME-D). Higher
concentrations of mAb were needed to induce CD16
modulation, CD54 upregulation, and ADCC on NK cells from
subjects with the lower affinity CD16 polymorphism. The
dose of mAb needed to induce NK activation was lower
with AME-D irrespective of CD16 polymorphism. At
saturating mAb concentrations, peak NK activation was
greater for AME-D. Similar results were found with
measurement of CD16 modulation, CD54 upregulation and
ADCC. These data demonstrate tumor cells coated with
mAb with enhanced affinity for CD16 are more effective
at activating NK cells at both low and saturating mAb
concentrations irrespective of CD16 polymorphism, and
provide further evidence for the clinical development of
such mAb with the goal of improving clinical response to
mAb.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Peipp, T. Schneider-Merck, M. Dechant, T. Beyer, J. J. Lammerts van Bueren, W. K. Bleeker, P. W. H. I. Parren, J. G. J. van de Winkel, and T. Valerius
Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations
J. Immunol.,
March 15, 2008;
180(6):
4338 - 4345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Congy-Jolivet, A. Bolzec, D. Ternant, M. Ohresser, H. Watier, and G. Thibault
Fc{gamma}RIIIa Expression Is Not Increased on Natural Killer Cells Expressing the Fc{gamma}RIIIa-158V Allotype
Cancer Res.,
February 15, 2008;
68(4):
976 - 980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Wang, E. Racila, R. P. Taylor, and G. J. Weiner
NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement
Blood,
February 1, 2008;
111(3):
1456 - 1463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Hatjiharissi, L. Xu, D. D. Santos, Z. R. Hunter, B. T. Ciccarelli, S. Verselis, M. Modica, Y. Cao, R. J. Manning, X. Leleu, et al.
Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIa-158 V/V and V/F polymorphism
Blood,
October 1, 2007;
110(7):
2561 - 2564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
