Treatment of Lymphoma With Radiolabeled Antibody: Elimination of Tumor Cells Lacking Target Antigen

Abstract

We have previously shown that ¹³¹ I-labeled monoclonal antibodies against the Thy1.1 differentiation antigen can induce the regression of Thy1.1 antigen-positive (Thy1.1 ⁺ ) AKR/J SL2T cell lymphoma nodules in AKR/Cum (Thy1.2 ⁺ ) mice. In this study, we examined the ability of ¹³¹ I-labled anti-thy1.1 antibodies to eliminate tumor nodules containing vairant lymphoma cells that do not express the Thy1.1 antigen (Thy1.1 ⁻ ). AKR/Cum mice were sc inoculated with mixtures of 1–2 × 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 μCi of ¹³¹ I-labled 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, nocomplete regressions were observed in mice with only antigen-negative tumor cells treated with ¹³¹ I-labled anti-thy1.1 antibody or in mice inoculated with antigen-positive tumor and treated with an ¹³¹ I-labled control antibody. Of the mice receiving mixtures containing 3%–10% antigen-negative cells, five of seven showed complete regression. These results demonstrate that radiolabled antibodies can eliminate small numbers of antigen-negative tumor cells present within a tumor mass. [J Natl Cancer Inst 82:47–50, 1990]