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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3688-3696. Prepublished online as a Blood First Edition Paper on August 3, 2004; DOI 10.1182/blood-2004-03-0963. This Article Full Text (PDF) All Versions of this Article: 2004-03-0963v1 104/12/3688    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 Tassone, P. Articles by Anderson, K. C Search for Related Content PubMed PubMed Citation Articles by Tassone, P. Articles by Anderson, K. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 12, 2004 Accepted July 9, 2004 Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ Multiple Myeloma cells Pierfrancesco Tassone, Victor S Goldmacher, Paola Neri, Antonella Gozzini, Masood A Shammas, Kathleen R Whiteman, Linda Hylander, Daniel R Carrasco, Teru Hideshima, Reshma Shringarpure, Jialan Shi, Charles K Allam, John Wijdenes, Salvatore Venuta, Nikhil C Munshi, and Kenneth C Anderson* Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA; Experimental and Clinical Medicine, University of 'Magna Gracia', Catanzaro, Italy ImmunoGen, Inc., Cambridge, MA, USA Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; Experimental and Clinical Medicine, University of 'Magna Gracia', Catanzaro, Italy Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA Diaclone research, Besancon cedex, France Experimental and Clinical Medicine, University of 'Magna Gracia', Catanzaro, Italy Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA * Corresponding author; email: Kenneth_Anderson{at}dfci.harvard.edu. We tested the in vitro and in vivo anti-tumor activity of the maytansinoid DM1, a potent antimicrotubule agent, covalently linked to the murine monoclonal antibody (mAb) B-B4 targeting syndecan-1 (CD138). We evaluated the in vitro activity of B-B4-DM1 against a panel of CD138+ and CD138- cell lines, as well as CD138+ patient multiple myeloma (MM) cells. Treatment with B-B4-DM1 selectively decreased growth and survival of MM cell lines, patient MM cells, and MM cells adherent to bone marrow stromal cells. We further examined the activity of B-B4-DM1 in three human MM models in mice: (i) SCID mice bearing subcutaneous xenografts; (ii) SCID mice bearing fluorescent GFP+ xenografts, and (iii) SCID mice implanted with human fetal bone (SCID-hu) and subsequently injected with patient MM cells. Tumor regression and inhibition of tumor growth, improvement in overall survival, and reduction in levels of circulating human paraprotein were observed in mice treated with B-B4-DM1. Although immunohistochemical analysis demonstrates restricted CD138 expression in human tissues, the lack of B-B4 reactivity with mouse tissues precludes evaluation of its toxicity in these models. In conclusion, B-B4-DM1 is a potent anti-MM agent which kills cells in an antigen-dependent manner in vitro and mediates in vivo anti-tumor activity at doses that are well tolerated, providing the rationale for clinical trials of this immunoconjugate in MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Laurent, C. Do, R. D. Gascoyne, L. Lamant, L. Ysebaert, G. Laurent, G. Delsol, and P. Brousset Anaplastic Lymphoma Kinase-Positive Diffuse Large B-Cell Lymphoma: A Rare Clinicopathologic Entity With Poor Prognosis J. Clin. Oncol., September 1, 2009; 27(25): 4211 - 4216. [Abstract] [Full Text] [PDF] A. M. Al-Katib, A. Aboukameel, R. Mohammad, M.-C. Bissery, and C. 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