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, Tim M. Illidge

    Research output: Contribution to journalArticlepeer-review


    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. © 2004 by The American Society of Hematology.
    Original languageEnglish
    Pages (from-to)1485-1494
    Number of pages9
    Issue number4
    Publication statusPublished - 15 Feb 2004


    • Animals
    • pharmacology: Antibodies, Monoclonal
    • immunology: Antigens, Surface
    • Combined Modality Therapy
    • Dose-Response Relationship, Radiation
    • Histocompatibility Antigens Class II
    • pharmacology: Iodine Radioisotopes
    • mortality: Lymphoma
    • Mice
    • Mice, Inbred BALB C
    • Mice, Inbred CBA
    • methods: Radioimmunotherapy
    • Research Support, Non-U.S. Gov't
    • immunology: Signal Transduction


    Dive into the research topics of 'Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy'. Together they form a unique fingerprint.

    Cite this