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Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy.

Abstract：

: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 (131)I-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 (131)I 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 (131)I 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.

journal_name

Blood

journal_title

Blood

authors

Du Y,Honeychurch J,Cragg MS,Bayne M,Glennie MJ,Johnson PW,Illidge TM

doi

10.1182/blood-2003-06-2037

subject

Has Abstract

pub_date

2004-02-15 00:00:00

pages

1485-94

issue

4

eissn

0006-4971

issn

1528-0020

pii

2003-06-2037

journal_volume

103

pub_type

杂志文章

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