EXPERIMENTAL RADIOTHERAPY OF MURINE LYMPHOMA WITH I-131-LABELED ANTI-THY 1.1 MONOCLONAL-ANTIBODY

Abstract

Monoclonal antibodies against the Thy 1.1 differentiation antigen are ineffective in the treatment of transplanted AKR T-cell lymphoma once a palpable tumor nodule is present, due to the inability of the host to eliminate antibody-coated tumor cells. To overcome this limitation, the use of 131I-labeled anti-Thy 1.1 antibodies for the therapy of established AKR/J SL2 lymphoma (Thy 1.1+) nodules growing in congeneic AKR/Cu mice (Thy 1.2+) was evaluated. In these experiments, 131I-anti-Thy 1.1 antibody specifically localized to a s.c. tumor with a mean of 6.5% of the infused dose per g of tumor at 24 h after infusion. The proportion of infused anti-Thy 1.1 antibody localizing to tumor was constant following antibody doses of up to 400 .mu.g/animal. Antibody iodinated with up to 2 atoms of I per antibody of molecule maintained binding activity and localization to tumor equivalent to antibody labeled with less I. The concentrations of 131I-anti-Thy 1.1 in tumor would result in delivery of a mean of 1600 cGY [greys] to tumor following infusion of 500 .mu.Ci of 131I-labeled anti-Thy 1.1 antibody. In comparison, 500 .mu.Ci 131I-labeled irrelevant antibody would deliver a mean of 380 cGy to tumor. Treatment of animals with palpable tumor nodules with 500 .mu.Ci 131I-anti-Thy 1.1 led to regression of the tumor nodule in 44% of animals, significantly prolonged survival and cured 2 of 5 of the animals treated prior to the development of metastatic disease. In contrast, unlabeled anti-Thy 1.1 led to tumor response in 6% of animals and up to 1000 .mu.Ci 131I-labeled irrelevant antibody had no effect on tumor growth. Therapy was limited by the emergence of variant tumor cells lacking the target antigen and by bone marrow toxicity following 131I-labeled antibody doses of .gtoreq. 1000 .mu.Ci/animal. 131I-Labeled monoclonal antibodies can have a significant antitumor effect in a situation where unmodified antibody is ineffective.