The importance of antibody-specificity in determining successful radioimmunotherapy of B-cell lymphoma

We report the radioimmunotherapy of mouse B-cell lymphoma, BCL1, using a pa nel of anti-B-cell monoclonal antibodies (MoAb) (anti-CD19, anti-CD22, anti -major histocompatibility complex (MHC) II, and anti-idiotype (Id) radiolab eled with 131-iodine. When administered early in disease (day 4), the I-131 -anti-MHCII MoAb cured tumors as a result of targeted irradiation alone, th e unlabeled MoAb being nontherapeutic. In contrast, I-131-anti-Id, despite targeting irradiation and having therapeutic activity as an unconjugated an tibody, protected mice for only 30 days; I-131-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 reducti on in therapeutic activity with the anti-MHCII, but surprisingly, allowed I -131-anti-Id to cure most mice. This unexpected potency of I-131-anti-Id la te in the disease appeared to result from the direct cytotoxicity of the an ti-Id MoAb, which was more active in established disease, in combination wi th 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. (C) 1999 by The American Society of Hematology.