Lysis of Autologous Tumor Cells by Peripheral Blood Lymphocytes Treated with Interleukin 2 in Patients with Renal Cell Carcinoma

Abstract

Peripheral blood lymphocytes derived from patients with renal cell carcinoma were stimulated with interleukin 2 and tested in a 4-hour 51chromium-release cytotoxicity assay against autologous cultured tumor and myeloid K562 cells. Of 23 patients autologous tumor lysis of more than 0 per cent was observed in 20 (range 5.3 to 82.8 per cent) and more than 10 per cent lysis was noted in 16. Since no significant correlation between the degree of cytotoxicity and the pathological findings of tumor stage, grade, cell type or lymphocyte infiltration in the tumor was found, it was impossible to predict from the pathological findings which tumor could be lysed by peripheral blood lymphocytes treated with interleukin 2. Comparison of natural killer cell activity against K562 of freshly prepared peripheral blood lymphocytes to that of interleukin 2-treated lymphocytes revealed significant augmentation from 23.6 ± 9.7 to 65.2 ± 29.1 per cent. From the kinetics study the lysis of autologous tumor cells was detectable on day 2 of interleukin 2 exposure and the peak activity was observed on day 5. A similar trend was noted in regard to K562 cell lysis. Measurements of peripheral blood lymphocyte subsets with monoclonal antibodies and argon ion laser flow cytometry resulted in a significant decrease of cells positive for OKT 4 (helper/inducer) and a significant increase of cells positive for OKT 8 (suppressor/cytotoxic) and Leu 7 (natural killer) by interleukin 2 treatment. A cold target cell inhibition test was performed in 2 patients with unlabeled autologous tumor and K562 cells as cold inhibitors. In 1 patient unlabeled K562 completely inhibited the tumor lysis but in 1 complete inhibition by autologous tumor and incomplete blockade by K562 were found. From this observation we concluded that peripheral blood lymphocytes treated with interleukin 2 lysed not only autologous tumor cells but also K562.Our results demonstrate that adoptive immunotherapy with peripheral blood lymphocytes activated by interleukin 2 in patients with renal cell carcinoma could be appropriate as a therapeutic procedure.