Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies

C. C. Badger, Kenneth Krohn, H. Shulman, N. Flournoy, I. D. Bernstein

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Abstract

We have shown previously that 131I-labeled antibodies against the Thy-1.1 differentiation antigen can cure AKR/Cum (Thy-1.2+) mice bearing AKR/J (Thy-1.1+) SL2 T-cell lymphoma. In the present study we have extended these studies to the therapy of SL2 lymphoma in AKR/J mice, where 131I-anti-labeled Thy-1.1 antibodies react with both tumor and normal T-lymphocytes. A single 25-μg bolus of 131I-labeled anti-Thy-1.1 antibody was rapidly cleared from serum by binding to spleen cells (t( 1/2 ) <3 h) and only low concentrations (131I-labeled antibody resulted in a tumor concentration of 9.7% injected dose/g 24 h after infusion of the radiolabeled antibody. With this latter regimen, biodistribution approximated that seen in AKR/Cum mice, and infusion of 1000 μCi would result in delivery of 16 Gy to tumor. Therapy of AKR/J mice bearing established s.c. lymphoma nodules with 1500 μCi of 131I-anti-Thy-1.1 antibody given in this latter regimen resulted in complete regression of the nodule in 70% of animals and had a greater antitumor effect (27% complete regression, P <0.001) than 750 μCi of 131I-labeled irrelevant antibody, a dose that would deliver equivalent radiation to normal organs (liver, kidney, and lung). The anti-Thy-1.1 antibody had only a slightly greater antitumor effect than an equivalent μCi dose (1500 μCi) of 131I-labeled control antibody (42% complete regression, P = 0.12). Both antibodies were marrow toxic and all animals treated with 1500 μCi died of marrow aplasia. These studies suggest that radiolabeled antibodies against differentiation antigens may be useful for therapy in spite of binding to normal cell populations but curative therapy may require infusion of unirradiated bone marrow.

Original languageEnglish (US)
Pages (from-to)6223-6228
Number of pages6
JournalCancer Research
Volume46
Issue number12 I
StatePublished - 1986
Externally publishedYes

Fingerprint

Radioimmunotherapy
Lymphoma
Inbred AKR Mouse
T-Lymphocytes
Antibodies
Bone Marrow
Differentiation Antigens
Thy-1 Antigens
Neoplasms
T-Cell Lymphoma
Poisons
Therapeutics
Thomsen-Friedenreich antibodies
Spleen
Radiation
Kidney
Lung
anti-Thy antibody
Liver
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Badger, C. C., Krohn, K., Shulman, H., Flournoy, N., & Bernstein, I. D. (1986). Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies. Cancer Research, 46(12 I), 6223-6228.

Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies. / Badger, C. C.; Krohn, Kenneth; Shulman, H.; Flournoy, N.; Bernstein, I. D.

In: Cancer Research, Vol. 46, No. 12 I, 1986, p. 6223-6228.

Research output: Contribution to journalArticle

Badger, CC, Krohn, K, Shulman, H, Flournoy, N & Bernstein, ID 1986, 'Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies', Cancer Research, vol. 46, no. 12 I, pp. 6223-6228.
Badger, C. C. ; Krohn, Kenneth ; Shulman, H. ; Flournoy, N. ; Bernstein, I. D. / Experimental radioimmunotherapy of murine lymphoma with 131I-labeled anti-T-cell antibodies. In: Cancer Research. 1986 ; Vol. 46, No. 12 I. pp. 6223-6228.
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abstract = "We have shown previously that 131I-labeled antibodies against the Thy-1.1 differentiation antigen can cure AKR/Cum (Thy-1.2+) mice bearing AKR/J (Thy-1.1+) SL2 T-cell lymphoma. In the present study we have extended these studies to the therapy of SL2 lymphoma in AKR/J mice, where 131I-anti-labeled Thy-1.1 antibodies react with both tumor and normal T-lymphocytes. A single 25-μg bolus of 131I-labeled anti-Thy-1.1 antibody was rapidly cleared from serum by binding to spleen cells (t( 1/2 ) <3 h) and only low concentrations (131I-labeled antibody resulted in a tumor concentration of 9.7{\%} injected dose/g 24 h after infusion of the radiolabeled antibody. With this latter regimen, biodistribution approximated that seen in AKR/Cum mice, and infusion of 1000 μCi would result in delivery of 16 Gy to tumor. Therapy of AKR/J mice bearing established s.c. lymphoma nodules with 1500 μCi of 131I-anti-Thy-1.1 antibody given in this latter regimen resulted in complete regression of the nodule in 70{\%} of animals and had a greater antitumor effect (27{\%} complete regression, P <0.001) than 750 μCi of 131I-labeled irrelevant antibody, a dose that would deliver equivalent radiation to normal organs (liver, kidney, and lung). The anti-Thy-1.1 antibody had only a slightly greater antitumor effect than an equivalent μCi dose (1500 μCi) of 131I-labeled control antibody (42{\%} complete regression, P = 0.12). Both antibodies were marrow toxic and all animals treated with 1500 μCi died of marrow aplasia. These studies suggest that radiolabeled antibodies against differentiation antigens may be useful for therapy in spite of binding to normal cell populations but curative therapy may require infusion of unirradiated bone marrow.",
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