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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1185-1192. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-07-034017. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-034017v1 109/3/1185    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 McEarchern, J. A. Articles by Law, C.-L. Search for Related Content PubMed PubMed Citation Articles by McEarchern, J. A. Articles by Law, C.-L. Related Collections Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities Julie A. McEarchern1, Ezogelin Oflazoglu1, Leigh Francisco1, Charlotte F. McDonagh1, Kristine A. Gordon1, Ivan Stone1, Kerry Klussman1, Eileen Turcott1, Nico van Rooijen2, Paul Carter1, Iqbal S. Grewal1, Alan F. Wahl1, and Che-Leung Law1 1 Seattle Genetics, Seattle, WA; 2 Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, the Netherlands Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of severe combined immunodeficient (SCID) mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages, and natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell–mediated antitumor activity and has potential utility for anticancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Oflazoglu, T. E. Boursalian, W. Zeng, A. C. Edwards, S. Duniho, J. A. McEarchern, C.-L. Law, H.-P. Gerber, and I. S. Grewal Blocking of CD27-CD70 Pathway by Anti-CD70 Antibody Ameliorates Joint Disease in Murine Collagen-Induced Arthritis J. Immunol., September 15, 2009; 183(6): 3770 - 3777. [Abstract] [Full Text] [PDF] J. A. McEarchern, L. M. Smith, C. F. McDonagh, K. Klussman, K. A. Gordon, C. A. Morris-Tilden, S. Duniho, M. Ryan, T. E. Boursalian, P. J. Carter, et al. Preclinical Characterization of SGN-70, a Humanized Antibody Directed against CD70 Clin. Cancer Res., December 1, 2008; 14(23): 7763 - 7772. [Abstract] [Full Text] [PDF] A. W. Ho, E. Hatjiharissi, B. T. Ciccarelli, A. R. Branagan, Z. R. Hunter, X. Leleu, O. Tournilhac, L. Xu, K. O'Connor, R. J. Manning, et al. CD27-CD70 interactions in the pathogenesis of Waldenstrom macroglobulinemia Blood, December 1, 2008; 112(12): 4683 - 4689. [Abstract] [Full Text] [PDF] H. M. Horton, M. J. Bernett, E. Pong, M. Peipp, S. Karki, S. Y. Chu, J. O. Richards, I. Vostiar, P. F. Joyce, R. Repp, et al. Potent In vitro and In vivo Activity of an Fc-Engineered Anti-CD19 Monoclonal Antibody against Lymphoma and Leukemia Cancer Res., October 1, 2008; 68(19): 8049 - 8057. [Abstract] [Full Text] [PDF] M. Baba, M. Okamoto, T. Hamasaki, S. Horai, X. Wang, Y. Ito, Y. Suda, and N. Arima Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells J. Virol., April 15, 2008; 82(8): 3843 - 3852. [Abstract] [Full Text] [PDF] A. K. Simon, T. Newsom-Davis, M. E. F. Frayne, P. F.-T. Ch'en, A. J. McMichael, and G. R. Screaton Generation of tumour-rejecting anti-carbohydrate monoclonal antibodies using melanoma modified with Fas ligand Int. Immunol., April 1, 2008; 20(4): 525 - 534. [Abstract] [Full Text] [PDF] E. Oflazoglu, I. J. Stone, K. A. Gordon, I. S. Grewal, N. van Rooijen, C.-L. Law, and H.-P. Gerber Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30 Blood, December 15, 2007; 110(13): 4370 - 4372. [Abstract] [Full Text] [PDF] M. C. Ryan, M. Hering, D. Peckham, C. F. McDonagh, L. Brown, K. M. Kim, D. L. Meyer, R. F. Zabinski, I. S. Grewal, and P. J. Carter Antibody targeting of B-cell maturation antigen on malignant plasma cells Mol. Cancer Ther., November 1, 2007; 6(11): 3009 - 3018. [Abstract] [Full Text] [PDF]

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