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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-03-0687. This Article Full Text (PDF) All Versions of this Article: 2002-03-0687v1 100/13/4574    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dechant, M. Articles by Valerius, T. Search for Related Content PubMed PubMed Citation Articles by Dechant, M. Articles by Valerius, T. Social Bookmarking                   What's this? Submitted March 6, 2002 Accepted July 22, 2002 Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing Michael Dechant, Gestur Vidarsson, Bernhard Stockmeyer, Roland Repp, Martin J Glennie, Martin Gramatzki, Jan G J van de Winkel, and Thomas Valerius* Department of Medicine III, Division of Hematology/Oncology, University Erlangen-Nuernberg, Erlangen, Germany Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Tenovus Research Laboratory, Southampton, United Kingdom Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Genmab, Utrecht, The Netherlands * Corresponding author; email: Thomas.Valerius{at}med3.imed.uni-erlangen.de. Antibodies against HLA class II, such as 1D10 or Lym-1, are currently evaluated for the treatment of B-cell lymphomas. Previous studies have demonstrated that - in addition to IgG Fc receptors - also the human myeloid IgA receptor (FcRI, CD89) effectively triggered tumor cell killing. Therefore, we have used the variable light and heavy chain sequences from another murine anti-HLA class II hybridoma, F3.3, to generate a panel of chimeric human/mouse antibodies, including human IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Antibody production was accomplished by stable transfection of baby hamster kidney cells, and binding activity and specificity was confirmed by ELISA and Western blotting. All constructs demonstrated similar binding to HLA class II. Functional studies revealed that chimeric IgG1, IgA1 and IgA2 triggered similar levels of tumor cell lysis. Analyses of effector populations, however, demonstrated that killing by chimeric IgG1 constructs was mainly triggered by human mononuclear cells and complement, while IgA1 and IgA2 mediated effective lysis by polymorphonuclear neutrophils. Importantly, IgG1 and both IgA isotypes were equally effective at killing freshly isolated human chronic lymphocytic leukemia cells. In conclusion, chimeric IgA antibodies against HLA class II may constitute attractive reagents for lymphoma therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. He, Q. Cao, Y. Qiu, J. Mi, J. Z. Zhang, M. Jin, H. Ge, S. G. Emerson, Y. Zhang, and Y. Zhang A New Approach to the Blocking of Alloreactive T Cell-Mediated Graft-versus-Host Disease by In Vivo Administration of Anti-CXCR3 Neutralizing Antibody J. Immunol., December 1, 2008; 181(11): 7581 - 7592. [Abstract] [Full Text] [PDF] J. E. Bakema, A. Bakker, S. de Haij, H. Honing, M. Bracke, L. Koenderman, G. Vidarsson, J. G. J. van de Winkel, and J. H. W. Leusen Inside-Out Regulation of Fc{alpha}RI (CD89) Depends on PP2A J. Immunol., September 15, 2008; 181(6): 4080 - 4088. [Abstract] [Full Text] [PDF] M. Dechant, T. Beyer, T. Schneider-Merck, W. Weisner, M. Peipp, J. G. J. van de Winkel, and T. Valerius Effector Mechanisms of Recombinant IgA Antibodies against Epidermal Growth Factor Receptor J. Immunol., September 1, 2007; 179(5): 2936 - 2943. [Abstract] [Full Text] [PDF] H. Horner, C. Frank, C. Dechant, R. Repp, M. Glennie, M. Herrmann, and B. Stockmeyer Intimate Cell Conjugate Formation and Exchange of Membrane Lipids Precede Apoptosis Induction in Target Cells during Antibody-Dependent, Granulocyte-Mediated Cytotoxicity J. Immunol., July 1, 2007; 179(1): 337 - 345. [Abstract] [Full Text] [PDF] M. A. Otten, E. Rudolph, M. Dechant, C. W. Tuk, R. M. Reijmers, R. H. J. Beelen, J. G. J. van de Winkel, and M. van Egmond Immature Neutrophils Mediate Tumor Cell Killing via IgA but Not IgG Fc Receptors J. Immunol., May 1, 2005; 174(9): 5472 - 5480. [Abstract] [Full Text] [PDF] J. L. Teeling, R. R. French, M. S. Cragg, J. van den Brakel, M. Pluyter, H. Huang, C. Chan, P. W. H. I. Parren, C. E. Hack, M. Dechant, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas Blood, September 15, 2004; 104(6): 1793 - 1800. [Abstract] [Full Text] [PDF]

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