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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1485-1494. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-06-2037. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2037v1 103/4/1485    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 Du, Y. Articles by Illidge, T. M. Search for Related Content PubMed PubMed Citation Articles by Du, Y. Articles by Illidge, T. M. Related Collections Immunobiology Neoplasia Signal Transduction Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy Yong Du, Jamie Honeychurch, Mark S. Cragg, Mike Bayne, Martin J. Glennie, Peter W. M. Johnson, and Tim M. Illidge From the Cancer Sciences Division, School of Medicine, Southampton University Hospital, Southampton, United Kingdom. Radioimmunotherapy (RIT) has emerged as an effective treatment for lymphoma, however the underlying mechanisms are poorly understood. We therefore investigated the relative contributions of antibody and targeted radiation to the clearance of tumor in vivo, using 2 different syngeneic murine B-cell lymphoma models. Although RIT with 131I–anti–major histocompatibility complex class II (MHCII) was effective in targeting radiation to tumor, no improvement in survival was seen by escalating the radiation dose alone and there were no long-term survivors. In contrast, using the combination of 131I anti-MHCII in the presence of unlabeled anti-idiotype (anti-Id), 100% prolonged disease-free survival was seen in both B-cell lymphoma models at the higher radiation dose. Using in vivo tracking we show that treatment with radiation plus anti-Id monoclonal antibody (mAb) results in a substantially greater reduction of splenic tumor cells than with either treatment alone. Prolonged survival could also be achieved using 131I anti-MHCII plus the signaling anti-CD19 mAb. Furthermore, the ability of these anti–B-cell mAbs to improve survival with targeted radiotherapy appeared to correlate with their ability to initiate intracellular signal transduction. Together these data illustrate that using 1 mAb to target radiation to tumor and a second to induce cell signaling is an effective new strategy in RIT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Martensson, R. Nilsson, T. Ohlsson, H.-O. Sjogren, S.-E. Strand, and J. Tennvall Reduced Myelotoxicity with Sustained Tumor Concentration of Radioimmunoconjugates in Rats after Extracorporeal Depletion J. Nucl. Med., February 1, 2007; 48(2): 269 - 276. [Abstract] [Full Text] [PDF] Y. Du, J. Honeychurch, M. Glennie, P. Johnson, and T. Illidge Microscopic Intratumoral Dosimetry of Radiolabeled Antibodies Is a Critical Determinant of Successful Radioimmunotherapy in B-Cell Lymphoma Cancer Res., February 1, 2007; 67(3): 1335 - 1343. [Abstract] [Full Text] [PDF] R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF] E. Mitrofanova, R. Unfer, N. Vahanian, W. Daniels, E. Roberson, T. Seregina, P. Seth, and C. Link Jr. Rat Sodium Iodide Symporter for Radioiodide Therapy of Cancer Clin. Cancer Res., October 15, 2004; 10(20): 6969 - 6976. [Abstract] [Full Text] [PDF]

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