EXPERIMENTAL RADIOIMMUNOTHERAPY OF MURINE LYMPHOMA WITH I-131-LABELED ANTI-T-CELL ANTIBODIES

Abstract

We have shown previously that 131I-labeled antibodies against the Thy-1.1 differentiation antigen can cure AKR/Cum (Thy-1.2+) mice bearing AKR/J (Thy-1.1+) SL2 T-cell lymphoma. In the present study we have extended these studies to the therapy of SL2 lymphoma in AKR/J mice, where 131I-anti-labeled Thy-1.1 antibodies react with both tumor and normal T-lymphocytes. A single 25-.mu.g bolus of 131I-labeled anti-Thy-1.1 antibody was rapidly cleared from serum by binding to spleen cells (t1/2 < 3h) and only low concentrations (<2% injected dose/g) were present in tumor 24 h after infusion. Doses of 0.5-5.0 mg antibody saturated cells in the spleen but only slightly increased the proportion of antibody in tumor. In contrast, pretreatment of mice with 1.0 mg of unlabeled anti-Thy-1.1 antibody 24 h prior to 131I-labeled antibody resulted in a tumor concentration of 9.7% injected dose/g 24 h after infusion of the radiolabeled antibody. With this latter regimen, biodistribution approximated that seen in AKR/Cum mice, and infusion of 1000 .mu.Ci would result in delivery of 16 Gy to tumor. Therapy of AKR/J mice bearing established s.c. lymphoma nodules with 1500 .mu.Ci of 131I-anti-Thy-1.1 antibody given in this latter regimen resulted in complete regression of the nodule in 70% of animals and had a greater antitumor effect (27% complete regression, P < 0.001) than 750 .mu.Ci of 131I-labeled irrelevant antibody, a dose that would deliver equivalent radiation to normal organs (liver, kidney, and lung). The anti-Thy-1.1 antibody had only a slightly greater antitumor effect than an equivalent .mu.Ci dose (1500 .mu.Ci) of 131I-labeled control antibody (42% complete regression, P=0.12). Both antibodies were marrow toxic and all animals treated with 1500 .mu.Ci died of marrow aplasia. These studies suggest that radiolabeled antibodies against differentiation antigens may be useful for therapy in spite of binding to normal cell populations but curative therapy may require infusion of unirradiated bone marrow.