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Experimental Radiotherapy of Murine Lymphoma with ¹³¹I-labeled Anti-Thy 1.1 Monoclonal Antibody¹

Programs in Medical Oncology [C. C. B., H. S.], Pediatric Oncology [I. D. B.], and Biostatistics [A. V. P.], Fred Hutchinson Cancer Research Center, and Departments of Medicine [C. C. B.], Radiology [K. A. K.], Biostatistics [A. V. P.], Pathology [H. S.], and Pediatrics [I. D. B.], University of Washington, Seattle, Washington 98104

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 µg/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 µCi of ¹³¹I-labeled anti-Thy 1.1 antibody. In comparison, 500 µCi ¹³¹I-labeled irrelevant antibody would deliver a mean of 380 cGy to tumor. Treatment of animals with palpable tumor nodules with 500 µCi 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 µCi 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 1000 µCi/animal. These studies demonstrate that ¹³¹I-labeled monoclonal antibodies can have a significant antitumor effect in a situation where unmodified antibody is ineffective.

¹ Supported in part by NIH Grant CA33477.

² Recipient of an American Cancer Society Junior Clinical Faculty Fellowship. To whom requests for reprints should be addressed, at Fred Hutchinson Cancer Research Center, 1124 Columbia St., Seattle, WA 98104.

Received 5/29/84. Revised 10/15/84. Revised 1/ 2/85. Accepted 1/ 3/85.

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