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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.
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.
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