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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 10, 2007 Accepted March 5, 2007 Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin's lymphoma Andrew G. Polson*, Shang-Fan Yu, Kristi Elkins, Bing Zheng, Suzanna Clark, Gladys S. Ingle, Dionysos S. Slaga, Lynne Giere, Changchun Du, Christine Tan, Jo-Anne Hongo, Alvin Gogineni, Mary J. Cole, Richard Vandlen, Jean-Philippe Stephan, Judy Young, Wesley Chang, Suzie J. Scales, Sarajane Ross, Dan Eaton, and Allen Ebens Department of Translational Oncology, Genentech, South San Francisco, CA, United States Department of Molecular Biology, Genentech, South San Francisco, CA, United States Department of Antibody Technology, Genentech, South San Francisco, CA, United States Department of Tumor Biology and Angiogenesis, Genentech, South San Francisco, CA, United States Department of Protein Chemistry, Genentech, South San Francisco, CA, United States Department of Assay Automation Technology, Genentech, South San Francisco, CA, United States Department of Pathology, Genentech, South San Francisco, CA, United States * Corresponding author; email: polson{at}gene.com. 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 (BCR), and are attractive targets for the use of ADCs since they are B-cell specific, expressed in non-Hodgkin's lymphomas (NHLs), and 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 NHL cell lines in vitro. Further, these two ADCs are equally effective at low doses in xenograft models of follicular, mantle cell, and Burkitt's 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 down-regulated surface BCR and were trafficked to the lysosomal-like 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. 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