Experimental radiotherapy of murine lymphoma with 131I-labeled anti-thy 1.1 monoclonal antibody

C. C. Badger, Kenneth Krohn, A. V. Peterson, H. Shulman, I. D. Bernstein

Research output: Contribution to journalArticle

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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 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, 131-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 concentations 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-labeled 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.

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

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Lymphoma
Radiotherapy
Monoclonal Antibodies
Neoplasms
Antibodies
Iodine
anti-Thy antibody
Thy-1 Antigens
Inbred AKR Mouse
Congenic Mice
Neoplasm Antibodies
T-Cell Lymphoma
Differentiation Antigens
Therapeutics
Bone Marrow
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Badger, C. C., Krohn, K., Peterson, A. V., Shulman, H., & Bernstein, I. D. (1985). Experimental radiotherapy of murine lymphoma with 131I-labeled anti-thy 1.1 monoclonal antibody. Cancer Research, 45(4), 1536-1544.

Experimental radiotherapy of murine lymphoma with 131I-labeled anti-thy 1.1 monoclonal antibody. / Badger, C. C.; Krohn, Kenneth; Peterson, A. V.; Shulman, H.; Bernstein, I. D.

In: Cancer Research, Vol. 45, No. 4, 1985, p. 1536-1544.

Research output: Contribution to journalArticle

Badger, CC, Krohn, K, Peterson, AV, Shulman, H & Bernstein, ID 1985, 'Experimental radiotherapy of murine lymphoma with 131I-labeled anti-thy 1.1 monoclonal antibody', Cancer Research, vol. 45, no. 4, pp. 1536-1544.
Badger, C. C. ; Krohn, Kenneth ; Peterson, A. V. ; Shulman, H. ; Bernstein, I. D. / Experimental radiotherapy of murine lymphoma with 131I-labeled anti-thy 1.1 monoclonal antibody. In: Cancer Research. 1985 ; Vol. 45, No. 4. pp. 1536-1544.
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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 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, 131-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 concentations 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-labeled 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.",
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