Treatment of lymphoma with radiolabeled antibody: elimination of tumor cells lacking target antigen.
We have previously shown that 131I-labeled monoclonal antibodies against the Thy1.1 differentiation antigen can induce the regression of Thy1.1 antigen-positive (Thy1.1+) AKR/J SL2 T cell lymphoma nodules in AKR/Cum (Thy1.2+) mice. In this study, we examined the ability of 131I-labeled anti-Thy1.1 antibodies to eliminate tumor nodules containing variant lymphoma cells that do not express the Thy1.1 antigen (Thy1.1-). AKR/Cum mice were sc inoculated with mixtures of 1-2 X 10(7) AKR/J SL2 cells and varying amounts (0.3%-10%) of Lsp3, a Thy1.1 antigen-negative (Thy1.1-) subclone of the SL2. One week later, when an established tumor nodule was present, mice were treated with 1,500-1,700 microCi of 131I-labeled anti-Thy1.1 antibody. Complete regression of tumor was observed in 11 of 12 (92%) mice inoculated with tumor containing 0.3%-1% antigen-negative cells. In contrast, no complete regressions were observed in mice with only antigen-negative tumor cells treated with 131I-labeled anti-Thy1.1 antibody or in mice inoculated with antigen-positive tumor and treated with an 131I-labeled control antibody. Of the mice receiving mixtures containing 3%-10% antigen-negative cells, five of seven showed complete regression. These results demonstrate that radiolabeled antibodies can eliminate small numbers of antigen-negative tumor cells present within a tumor mass.
Nourigat
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Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Badger
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Bernstein
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ID
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000032:analysis*; D004306:Dose-Response Relationship, Immunologic; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007518:Isoantibodies / Q000627:therapeutic use*; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009362:Neoplasm Metastasis; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007457:Iodine Radioisotopes; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody