Expansion of activated T-lymphocytes in patients treated with recombinant interleukin 2

Jonathan E. Kolitz, Karl Welte, George Y. Wong, Karen Holloway, Vincent J. Merluzzi, Adelheid Engert, Edward C. Bradley, Michael Konrad, Andrej Polivka, Janice L. Gabrilove, Karl W. Sykora, Glen A. Miller, Walter Fiedler, Susan Krown, Herbert F. Oettgen, Roland Mertelsmann

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18 Scopus citations

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 × 106 U/m2, with dose-limiting toxicity consisting of fever, diarrhea, and thrombocytopenia. At a well-tolerated dose of 1 × 106 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 × 106 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 α-interferon, no other lymphokines (β- and γ-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.

Original languageEnglish
Pages (from-to)412-429
Number of pages18
JournalJournal of Biological Response Modifiers
Volume6
Issue number4
StatePublished - Aug 1987
Externally publishedYes

Keywords

  • Cytotoxicity
  • IgG antibodies
  • Interleukin 2
  • Kaposi’s sarcoma
  • T cell growth
  • Tumor targets

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