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, we have evaluated 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+). 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 micrograms/animal. Antibody iodinated with up to 2 atoms of
iodine per antibody of molecule maintained binding activity and localization to
tumor equivalent to antibody labeled with less
iodine. The concentrations of 131I-anti-Thy 1.1 in
tumor would result in delivery of a mean of 1600 cGy to
tumor following infusion of 500 muCi of 131I-labeled
anti-Thy 1.1 antibody. In comparison, 500 muCi 131I-labeled irrelevant antibody would deliver a mean of 380 cGy to
tumor. Treatment of animals with palpable
tumor nodules with 500 muCi 131I-anti-Thy 1.1 led to regression of the
tumor nodule in 44% of animals, significantly prolonged survival, and cured two of five 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 muCi 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 greater than or equal to 1000 muCi/animal. These studies demonstrate that 131I-labeled
monoclonal antibodies can have a significant antitumor effect in a situation where unmodified antibody is ineffective.