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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 (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 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 Social Bookmarking                   What's this? Submitted June 23, 2003 Accepted October 15, 2003 Antibody induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy Yong Du, Jamie Honeychurch, Mark S Cragg, Mike C Bayne, Martin J Glennie, Peter W Johnson, and Tim M Illidge* Cancer Sciences Division, Southampton University, Southampton, Hampshire, United Kingdom * Corresponding author; email: tmi{at}soton.ac.uk. 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 tumour in vivo, using two different syngeneic murine B-cell lymphoma models. Although RIT with 131I-anti-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 (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 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 mAb to improve survival with targeted radiotherapy appeared to correlate with their ability to initiate intracellular signal transduction. Together these data illustrate that using one 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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