Expansion of activated T-lymphocytes in patients treated with recombinant interleukin 2.
Academic Article
Overview
abstract
Recombinant interleukin 2 (rIL 2, Cetus) was administered in escalating doses to 30 patients with advanced malignancy, including 14 patients with the epidemic form of Kaposi's sarcoma, in 2 week treatment cycles as a 6 h i.v. infusion for 10 doses. The maximum tolerated dose was 2 X 10(6) U/m2, with dose-limiting toxicity consisting of fever, diarrhea, and thrombocytopenia. At a well-tolerated dose of 1 X 10(6) U/m2, serum levels of rIL 2 of 30 U/ml were maintained for the duration of the infusion. Such concentrations sustain IL 2-dependent T cell growth in vitro. We observed a significant lymphocytosis in patients receiving 1 X 10(6) U/m2 of rIL 2 following 2 weeks of treatment (p = 0.0035). The expanded T cell pool was polyclonal, as demonstrated by increases in both T4+ and T8+ T cell subsets, and activated, with statistically significant increases in IL 2 receptor (p = 0.043), in the absence of transferrin receptor induction. Proliferating cells were not detected in peripheral blood using flow cytometry. Except for alpha-interferon, no other lymphokines (beta- and gamma-interferon, tumor necrosis factor) were present in serum during treatment. Reversible rises in anti-rIL 2 IgG antibodies occurred, as measured using an enzyme-linked immunosorbent assay. No changes were observed in the T cell mitogenic response to OKT3 and phytohemagglutinin, and no enhancement of cytotoxicity against natural killer-sensitive and resistant targets developed as a consequence of treatment. Except for a partial response in a patient with a myelodysplastic syndrome, no antitumor activity was observed. The in vivo expansion of T cells with the capacity to respond to rIL 2 with enhanced in vitro cytotoxicity against tumor targets provides impetus to ongoing trials exploring different routes and schedules of administration of rIL 2.
