Radioimmunotherapy in the pi-BCL1 B cell lymphoma model: efficacy depends on more than targeted irradiation alone.

作者: Timothy Illidge , Jamie Honeychurch , Anthony Vandersteen , Mark Cragg

DOI: 10.1089/CBR.2000.15.581

关键词: ImmunotherapyB-cell lymphomaAntigenRadioimmunotherapyImmunologyCD19Monoclonal antibodyIn vivoCancer researchMedicineIdiotype

摘要: We report the in vivo radioimmunotherapy (RIT) of a new variant BCL1 syngeneic mouse B-cell lymphoma model, pi-BCL1, using panel monoclonal antibodies (MoAb) reactive with B cell-associated antigens (CD19, CD22, CD40, MHC II, and idiotype). MoAb were radiolabeled 131I or used conjunction external beam irradiation. When administered early disease (day 4) 131I-anti-MHC II produced long term free survivors as result targeted irradiation alone; equivalent unlabelled was non-therapeutic. In contrast, 131I-anti-CD40, 131I-anti-Idiotype (Id) at day 4 despite targeting having intrinsic therapeutic activity unconjugated antibodies, protected mice for approximately 30 days. The 131I-anti-CD19 anti-CD22 therapeutically inactive. Treating later 14, after tumor inoculation) permitted study efficacy presence an increased load. An burden brought about expected reduction but surprisingly, anti-CD40 131I-anti-Id able to produce prolonged survival most mice. This unexpected potency 131I-anti-CD40 late appeared from direct cytotoxic action induced by these MoAb. Mechanisms which two operate, producing long-term animals advanced appear different. Our results have important implications selection reagents RIT demonstrate that successful treatment such agents may involve more than simple

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