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Blood, 15 July 2007, Vol. 110, No. 2, pp. 616-623. Prepublished online as a Blood First Edition Paper on March 20, 2007; DOI 10.1182/blood-2007-01-066704. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-01-066704v1 110/2/616    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 Polson, A. G. Articles by Ebens, A. Search for Related Content PubMed PubMed Citation Articles by Polson, A. G. Articles by Ebens, A. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma Andrew G. Polson1, Shang-Fan Yu1, Kristi Elkins1, Bing Zheng1, Suzanna Clark1, Gladys S. Ingle2, Dionysos S. Slaga1, Lynne Giere1, Changchun Du1, Christine Tan3, Jo-Anne Hongo3, Alvin Gogineni4, Mary J. Cole4, Richard Vandlen5, Jean-Philippe Stephan6, Judy Young6, Wesley Chang7, Suzie J. Scales2, Sarajane Ross1, Dan Eaton5, and Allen Ebens1 Departments of1 Translational Oncology 2 Molecular Biology 3 Antibody Technology 4 Tumor Biology and Angiogenesis 5 Protein Chemistry 6 Assay Automation Technology, and 7 Pathology, Genentech, South San Francisco, CA Targeting cytotoxic drugs to cancer cells using antibody–drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell–specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II–positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Zheng, R. N. Fuji, K. Elkins, S.-F. Yu, F. K. Fuh, J. Chuh, C. Tan, J.-A. Hongo, H. Raab, K. R. Kozak, et al. In vivo effects of targeting CD79b with antibodies and antibody-drug conjugates Mol. Cancer Ther., October 1, 2009; 8(10): 2937 - 2946. [Abstract] [Full Text] [PDF] D. Dornan, F. Bennett, Y. Chen, M. Dennis, D. Eaton, K. Elkins, D. French, M. A. T. Go, A. Jack, J. R. Junutula, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma Blood, September 24, 2009; 114(13): 2721 - 2729. [Abstract] [Full Text] [PDF] A. M. Al-Katib, A. Aboukameel, R. Mohammad, M.-C. Bissery, and C. Zuany-Amorim Superior Antitumor Activity of SAR3419 to Rituximab in Xenograft Models for Non-Hodgkin's Lymphoma Clin. Cancer Res., June 15, 2009; 15(12): 4038 - 4045. [Abstract] [Full Text] [PDF] H.-P. Gerber, M. Kung-Sutherland, I. Stone, C. Morris-Tilden, J. Miyamoto, R. McCormick, S. C. Alley, N. Okeley, B. Hayes, F. J. Hernandez-Ilizaliturri, et al. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas Blood, April 30, 2009; 113(18): 4352 - 4361. [Abstract] [Full Text] [PDF] R. M. Young, I. R. Hardy, R. L. Clarke, N. Lundy, P. Pine, B. C. Turner, T. A. Potter, and Y. Refaeli Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target Blood, March 12, 2009; 113(11): 2508 - 2516. [Abstract] [Full Text] [PDF] D. Jackson, J. Gooya, S. Mao, K. Kinneer, L. Xu, M. Camara, C. Fazenbaker, R. Fleming, S. Swamynathan, D. Meyer, et al. A Human Antibody-Drug Conjugate Targeting EphA2 Inhibits Tumor Growth In vivo Cancer Res., November 15, 2008; 68(22): 9367 - 9374. [Abstract] [Full Text] [PDF] Y. Li, F. Chen, M. Putt, Y. K. Koo, M. Madaio, J. C. Cambier, P. L. Cohen, and R. A. Eisenberg B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice J. Immunol., September 1, 2008; 181(5): 2961 - 2972. [Abstract] [Full Text] [PDF] W. Y. Lin, Q. Gong, D. Seshasayee, Z. Lin, Q. Ou, S. Ye, E. Suto, J. Shu, W. Pun Lee, C.-W. V. Lee, et al. Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade Blood, December 1, 2007; 110(12): 3959 - 3967. [Abstract] [Full Text] [PDF]

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