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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1807-1814. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-07-2466. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2466v1 103/5/1807    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 DiJoseph, J. F. Articles by Damle, N. K. Search for Related Content PubMed PubMed Citation Articles by DiJoseph, J. F. Articles by Damle, N. K. Related Collections Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies John F. DiJoseph, Douglas C. Armellino, Erwin R. Boghaert, Kiran Khandke, Maureen M. Dougher, Latha Sridharan, Arthur Kunz, Philip R. Hamann, Boris Gorovits, Chandrasekhar Udata, Justin K. Moran, Andrew G. Popplewell, Sue Stephens, Philip Frost, and Nitin K. Damle From the Departments of Oncology Discovery, Chemical Sciences, Drug Metabolism, and Bioprocess Development, Wyeth Research, Pearl River, NY; and the Department of Research and Development, Celltech, Slough, United Kingdom. Antibody-targeted chemotherapy with gemtuzumab ozogamicin (CMA-676, a CD33-targeted immunoconjugate of N-acetyl--calicheamicin dimethyl hydrazide [CalichDMH], a potent DNA-binding cytotoxic antitumor antibiotic) is a clinically validated therapeutic option for patients with acute myeloid leukemia (AML). Here, we describe the preclinical profile of another immunoconjugate of CalichDMH, CMC-544, targeted to CD22 expressed by B-lymphoid malignancies. CMC-544 comprises a humanized IgG4 anti-CD22 monoclonal antibody (mAb), G5/44, covalently linked to CalichDMH via an acid-labile 4-(4'-acetylphenoxy) butanoic acid (AcBut) linker. Both CMC-544 and unconjugated G5/44 bound human CD22 with subnanomolar affinity. CMC-544, but not unconjugated G5/44, exerted potent cytotoxicity against CD22+ B-cell lymphoma (BCL) cell lines (inhibitory concentration of 50%: 6-600 pM CalichDMH). CMC-544 caused a potent inhibition of growth of small but established BCL xenografts leading to cures (therapeutic index > 10). CMC-544 prevented the establishment of BCL xenografts and also caused regression of large BCLs (> 1.5 g tumor mass). In contrast, unconjugated CalichDMH, unconjugated G5/44, and an isotype-matched control conjugate, CMA-676, were ineffective against these BCL xenografts. Thus, CD22-targeted delivery of CalichDMH is a potent and effective preclinical therapeutic strategy for BCLs. The strong antitumor profile of CMC-544 supports its clinical evaluation as a treatment option for B-lymphoid malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Al-Katib, A. Aboukameel, R. Mohammad, M.-C. Bissery, and C. Zuany-Amorim Superior Antitumor Activity of SAR3419 to Rituximab in Xenograft Models for Non-Hodgkin's Lymphoma Clin. Cancer Res., June 15, 2009; 15(12): 4038 - 4045. [Abstract] [Full Text] [PDF] P. Martin, R. R. Furman, M. Coleman, and J. P. Leonard Phase I to III Trials of Anti B Cell Therapy in Non Hodgkin's Lymphoma Clin. Cancer Res., September 15, 2007; 13(18): 5636s - 5642s. [Abstract] [Full Text] [PDF] A. G. Polson, S.-F. Yu, K. Elkins, B. Zheng, S. Clark, G. S. Ingle, D. S. Slaga, L. Giere, C. Du, C. Tan, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma Blood, July 15, 2007; 110(2): 616 - 623. [Abstract] [Full Text] [PDF] J. F. DiJoseph, M. M. Dougher, L. B. Kalyandrug, D. C. Armellino, E. R. Boghaert, P. R. Hamann, J. K. Moran, and N. K. Damle Antitumor Efficacy of a Combination of CMC-544 (Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of Calicheamicin, and Rituximab against Non-Hodgkin's B-Cell Lymphoma Clin. Cancer Res., January 1, 2006; 12(1): 242 - 249. [Abstract] [Full Text] [PDF] K. Dunussi-Joannopoulos, G. E. Hancock, A. Kunz, M. Hegen, X. X. Zhou, B. J. Sheppard, J. Lamothe, E. Li, H.-L. Ma, P. R. Hamann, et al. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model Blood, October 1, 2005; 106(7): 2235 - 2243. [Abstract] [Full Text] [PDF] D. G. Maloney Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines J. Clin. Oncol., September 10, 2005; 23(26): 6421 - 6428. [Abstract] [Full Text] [PDF] J. F. DiJoseph, M. E. Goad, M. M. Dougher, E. R. Boghaert, A. Kunz, P. R. Hamann, and N. K. Damle Potent and Specific Antitumor Efficacy of CMC-544, a CD22-Targeted Immunoconjugate of Calicheamicin, against Systemically Disseminated B-Cell Lymphoma Clin. Cancer Res., December 15, 2004; 10(24): 8620 - 8629. [Abstract] [Full Text] [PDF] E. R. Boghaert, L. Sridharan, D. C. Armellino, K. M. Khandke, J. F. DiJoseph, A. Kunz, M. M. Dougher, F. Jiang, L. B. Kalyandrug, P. R. Hamann, et al. Antibody-Targeted Chemotherapy with the Calicheamicin Conjugate hu3S193-N-Acetyl {gamma} Calicheamicin Dimethyl Hydrazide Targets Lewisy and Eliminates Lewisy-Positive Human Carcinoma Cells and Xenografts Clin. Cancer Res., July 1, 2004; 10(13): 4538 - 4549. [Abstract] [Full Text] [PDF]

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