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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 233-243
The Importance of Antibody-Specificity in Determining Successful
Radioimmunotherapy of B-Cell Lymphoma
Timothy M. Illidge,
Mark S. Cragg,
Harry M. McBride,
Ruth R. French, and
Martin J. Glennie
From the Tenovus Research Laboratory, Southampton University
Hospitals, Southampton, UK.
We report the radioimmunotherapy of mouse B-cell lymphoma,
BCL1, using a panel of anti-B-cell monoclonal antibodies
(MoAb) (anti-CD19, anti-CD22, anti-major histocompatibility complex
(MHC) II, and anti-idiotype (Id) radiolabeled with 131-iodine. When administered early in disease (day 4), the 131I-anti-MHCII
MoAb cured tumors as a result of targeted irradiation alone, the
unlabeled MoAb being nontherapeutic. In contrast,
131I-anti-Id, despite targeting irradiation and having
therapeutic activity as an unconjugated antibody, protected mice for
only 30 days; 131I-anti-CD19 and anti-CD22 were
therapeutically inactive. Binding and biodistribution studies showed
that the anti-Id, unlike anti-MHCII, MoAb was cleared from target cells
in vivo and delivered 4 times less irradiation to splenic tumor.
Treating later in the disease (day 14) increased tumor load and
produced the expected reduction in therapeutic activity with the
anti-MHCII, but surprisingly, allowed 131I-anti-Id to cure
most mice. This unexpected potency of 131I-anti-Id late in
the disease appeared to result from the direct cytotoxicity of the
anti-Id MoAb, which was more active in established disease, in
combination with targeted irradiation. We believe the ability of
targeted irradiation and certain cytotoxic MoAb to work cooperatively
against tumor in this way has important implications for the selection
of reagents in radioimmunotherapy of B-cell lymphoma.
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