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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3705-3711. Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-03-0890. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0890v1 104/12/3705    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 Stein, R. Articles by Goldenberg, D. M. Search for Related Content PubMed PubMed Citation Articles by Stein, R. Articles by Goldenberg, D. M. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies Rhona Stein, Zhengxing Qu, Thomas M. Cardillo, Susan Chen, Adriane Rosario, Ivan D. Horak, Hans J. Hansen, and David M. Goldenberg From the Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ; and Immunomedics, Inc, Morris Plains, NJ. The humanized anti-CD74 monoclonal antibody (mAb) hLL1 is under evaluation as a therapeutic agent. The effects of hLL1—at times in comparison with the CD20 mAb rituximab—were assessed on non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) cell lines and in tumor-bearing SCID mice. In vitro, hLL1 caused growth inhibition and induction of apoptosis in B-cell lines when cross-linked with an antihuman immunoglobulin G (IgG) second antibody. The sensitivity profile of the cell lines was different for hLL1 and rituximab, and antiproliferative activity was augmented when the 2 mAbs were combined. Unlike rituximab, hLL1 did not induce antibody-dependent cellular cytotoxicity or complement-mediated cytotoxicity. In xenograft models of NHL and MM, treatment with hLL1 yielded significant survival benefits without cross-linking agents. Efficacy was greater in the MM model, in which median survival time was increased more than 4.5-fold. Thus, hLL1 has therapeutic potential as a naked mAb for B-cell malignancies because of high antigen expression on malignant cells, specifically MM, with limited expression on normal tissue, and because of its antiproliferative activity. Further, hLL1 may be a therapeutic candidate for rituximab-resistant disease because the 2 antibodies apparently act through distinct mechanisms and exhibit different expression and sensitivity profiles, and activity can be augmented when the mAbs are combined. 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