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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2211-2219. Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-08-110072. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-08-110072v1 111/4/2211    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 Qu, Z. Articles by Chang, C.-H. Search for Related Content PubMed PubMed Citation Articles by Qu, Z. Articles by Chang, C.-H. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Bispecific anti-CD20/22 antibodies inhibit B-cell lymphoma proliferation by a unique mechanism of action Zhengxing Qu1, David M. Goldenberg1,2, Thomas M. Cardillo1, Victoria Shi1, Hans J. Hansen1, and Chien-Hsing Chang1 1 Immunomedics, Morris Plains, NJ; and 2 Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ Combination immunotherapy with anti-CD20 and anti-CD22 mAbs shows promising activity in non-Hodgkin lymphoma. Therefore, bispecific mAbs (bsAbs) were recombinantly constructed from veltuzumab (humanized anti-CD20) and epratuzumab (humanized anti-CD22) and evaluated in vitro and in vivo. While none of the parental mAbs alone or mixed had notable antiproliferative activity against Burkitt lymphoma cells when not cross-linked, the bsAbs [eg, anti-CD20 IgG-anti–CD22 (scFv)2] were inhibitory without cross-linking and synergistic with B-cell antigen (BCR)-mediated inhibition. The bsAbs demonstrated higher antibody-dependent cellulary cytoxicity (ADCC) activity than the parental mAbs, but not complement-dependent cytoxicity (CDC) of the parental CD20 mAb. Cross-linking both CD20 and CD22 with the bsAbs resulted in the prominent redistribution of not only CD20 but also CD22 and BCR into lipid rafts. Surprisingly, appreciable translocation of CD22 into lipid rafts was also observed after treatment with epratuzumab. Finally, the bsAbs inhibited Daudi lymphoma transplant growth, but showed a significant advantage over the parental anti-CD20 mAb only at the highest dose tested. These results suggest that recombinantly fused, complementary, bispecific, anti-CD20/22 antibodies exhibit functional features distinct from their parental antibodies, perhaps representing new candidate therapeutic molecules. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. A. Rossi, D. M. Goldenberg, T. M. Cardillo, R. Stein, and C.-H. Chang Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma Blood, June 11, 2009; 113(24): 6161 - 6171. [Abstract] [Full Text] [PDF] E. A. Rossi, D. M. Goldenberg, T. M. Cardillo, R. Stein, Y. Wang, and C.-H. Chang Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics Cancer Res., October 15, 2008; 68(20): 8384 - 8392. [Abstract] [Full Text] [PDF]

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