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

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