Activation of Human T Cells Obtained Pre- and Post-Interleukin-2 (IL-2) Therapy by Anti-CD3 Monoclonal Antibody plus IL-2: Implications for Combined In Vivo Treatment

Gilda Weil-Hillman, Kathleen Schell, David M. Segal, Jacquelyn A. Hank, Jeffrey A. Sosman, Paul M. Sondel*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The role of activated T cells in the mediation of antitumor responses has been documented in several experimental models. In some of these, interleukin-2 (IL-2) has been used as a means to induce and expand the antitumor effects of the T cells. IL-2 has been tested in clinical trials for cancer treatment. Surprisingly, T cells appear to be inactivated by IL-2 in these clinical trials. T cells obtained from peripheral blood after IL-2 therapy showed decreased responses to mitogens and alloantigens, did not proliferate in vitro in response to IL-2, and did not mediate non-major histocompatibility complex-restricted cytotoxicity or targeted lysis in the presence of bispecific monoclonal antibodies. In this study, we present evidence that these post-IL-2 therapy T cells are not irreversibly inactivated; they can be activated in vitro by anti-CD3 monoclonal antibody together with IL-2 to upregulate the p55 component of the IL-2 receptor and proliferate. Nevertheless, following activation by anti-CD3 and IL-2, the level of targeted T-cell cytotoxicity mediated by the post-IL-2 therapy T cells was significantly lower than that by pre-IL-2 therapy T cells. Although in vivo treatment with IL-2 alone induces natural killer (NK) cells to mediate lymphokine-activated killer activity, these data suggest that the T-cell lytic function is inhibited by this treatment and only partially reversible by subsequent T-cell receptor activation using anti-CD3 mAb. Exposure of T cells to anti-CD3 mAb prior to in vivo IL-2 treatment generates T-cell lytic activity in vitro. These results, together with preclinical murine studies, suggest that a combined in vivo protocol of anti-CD3 mAb and IL-2, starting first with the anti-CD3 mAb, may cause activation of the T cells in addition to the activation of NK cells and thus warrant clinical testing.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalJournal of Immunotherapy
Volume10
Issue number4
DOIs
StatePublished - Aug 1991

Keywords

  • Activated T cells
  • Anti-CD3 monoclonal antibody
  • Interleukin-2
  • Lymphokine-activated killer cells
  • Natural killer cells
  • Peripheral blood lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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