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Blood, 11 June 2009, Vol. 113, No. 24, pp. 6161-6171. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2008-10-187138. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-10-187138v1 113/24/6161    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 CrossRef Google Scholar Articles by Rossi, E. A. Articles by Chang, C.-H. PubMed PubMed Citation Articles by Rossi, E. A. Articles by Chang, C.-H. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma Edmund A. Rossi1, David M. Goldenberg2, Thomas M. Cardillo3, Rhona Stein2, and Chien-Hsing Chang1,3 1 IBC Pharmaceuticals, Morris Plains, NJ; 2 Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, NJ; and 3 Immunomedics, Morris Plains, NJ The dock and lock (DNL) method is a new technology for generating multivalent antibodies. Here, we report in vitro and in vivo characterizations of 20-22 and 22-20, a pair of humanized hexavalent anti-CD20/22 bispecific antibodies (bsAbs) derived from veltuzumab (v-mab) and epratuzumab (e-mab). The 22-20 was made by site-specific conjugation of e-mab to 4 Fabs of v-mab; 20-22 is of the opposite configuration, composing v-mab and 4 Fabs of e-mab. Each bsAb translocates both CD22 and CD20 into lipid rafts, induces apoptosis and growth inhibition without second-antibody crosslinking, and is significantly more potent in killing lymphoma cells in vitro than their parental antibodies. Although both bsAbs triggered antibody-dependent cellular toxicity, neither displayed complement-dependent cytotoxicity. Intriguingly, 22-20 and 20-22 killed human lymphoma cells in preference to normal B cells ex vivo, whereas the parental v-mab depleted malignant and normal B cells equally. In vivo studies in Daudi tumors revealed 20-22, despite having a shorter serum half-life, had antitumor efficacy comparable with equimolar v-mab; 22-20 was less potent than 20-22 but more effective than e-mab and control bsAbs. These results indicate multiple advantages of hexavalent anti-CD20/22 bsAbs over the individual parental antibodies and suggest that these may represent a new class of cancer therapeutics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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