Experimental Radiotherapy of Murine Lymphoma with 131l-labeled Anti-Thy 1.1 Monoclonal Antibody

Christopher C. Badger, Kenneth A. Krohn, Arthur V. Peterson, Howard Shulman, Irwin D. Bernstein

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98 Scopus citations

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, we have evaluated the use of 1311-labeied 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, 131l-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 pgl 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 131l-anti-Thy 1.1 in tumor would result in delivery of a mean of 1600 cGy to tumor following infusion of 500 μ Ci of 131Wabeled anti-Thy 1.1 antibody. In comparison, 500 μ Ci 131Wabeled irrelevant antibody would deliver a mean of 380 cGy to tumor. Treatment of animals with palpable tumor nodules with 500 /μ Ci 131l-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 μ Ci 131Mabeled 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 131Mabeled antibody closes of ≥1000 μ Ci/animal. These studies demonstrate that 131l-labeled monoclonal antibodies can have a significant antitumor effect in a situation where unmodified antibody is ineffective.

Original languageEnglish (US)
Pages (from-to)1536-1544
Number of pages9
JournalCancer Research
Volume45
Issue number4
StatePublished - Apr 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Badger, C. C., Krohn, K. A., Peterson, A. V., Shulman, H., & Bernstein, I. D. (1985). Experimental Radiotherapy of Murine Lymphoma with 131l-labeled Anti-Thy 1.1 Monoclonal Antibody. Cancer Research, 45(4), 1536-1544.