CLINICAL AND IMMUNOLOGICAL STUDIES IN ADVANCED CANCER-PATIENTS SEQUENTIALLY TREATED WITH ANTI CD3 MONOCLONAL-ANTIBODY (OKT3) AND INTERLEUKIN-2

CD3 engagement has been used as a surrogate for antigen-specific stimu lation to trigger T cell effector functions. Exogenous IL-2 has been u sed to prolong and amplify CD3-induced T cell activation. Previous stu dies have shown that CD3 reactivity is increased in cancer patients wi th preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In th is study, we report 9 courses of a single infusion of anti-CDS mAb (OK T3) followed by continuos infusion of intermediate dose IL-2 in 4 canc er patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metas tatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells i n the peripheral blood. An increase of lymphocytes, equally distribute d between CD4+ and CD8+ subsets, was observed during treatment. Activa tion was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including prol iferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL -2 infusions were well tolerated and no limiting toxicity was observed . The treatment did not revert tumor progression in the 2 patients wit h progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequenti al administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for tr eatment because of an increased number of HLA-DR+ T cells in the perip heral blood. A discrepancy was observed between the emergence of CD25 T cells and the clinical outcome.