Clinical and Immunological Effects of Treatment with Murine Anti-Cd3 Monoclonal Antibody Along with Interleukin 2 in Patients with Cancer

Jacquelyn A. Hank*, Mark Albertini, Osvaldo H. Wesly, Joan H. Schiller, Aggie Borchert, Karen Moore, Robin Bechhofer, Barry Storer, Jacek Gan, Carlo Gambacorti, Jeffrey Sosman, Paul M. Sondel

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients with cancer. The anti-CD3 was given as an i.v. bolus infusion over 10 min followed by two i.v. 96-h continuous infusions of IL-2 at 3 x 106 units/ m2/day with a 3-day rest between the IL-2 infusions. Four patients were treated with 6, 18, 60, and 300 xg/m2 anti- CD3. One patient received 3000 (Jig/m2 anti-CD3. This patient developed profound hypotension and the IL-2 infusions were delayed for 2 weeks. Two patients were treated at an intermediate dose of 600 μg/m2. These patients developed dose-limiting toxicities including hypotension, dyspnea and increased blood urea nitrogen, creatinine, and bilirubin. They were unable to complete their first course of therapy. In an effort to achieve a dose of anti-CD3 which would activate T cells in vivo, pentoxifylline was given to blunt the toxicities seen with anti-CD3 thought to be due predominantly to the cytokine syndrome and tumor necrosis factor release. Four patients received p.o. pentoxifylline to cover an anti-CD3 dose of 600 ftg/m2. The IL-2 infusion was initiated 1 week after the mAb. While there was an anti-CD3 dose- dependent increase in serum tumor necrosis factor level 1 h after mAb infusion, pentoxifylline did not reduce the serum tumor necrosis factor level. There was also an anti-CD3 dose-dependent increase in the serum soluble IL-2 receptor levels. Other immune parameters monitored, including in vitro cytotoxic and proliferative responses and lymphocyte count, were similar to treatment courses with IL-2 alone. Fourteen of 26 patients examined developed human antimurine antibodies following a single dose of anti-CD3. There were no objective antitumor responses. We conclude that in vivo treatment with anti-CD3 did not enhance T cell activity or expansion with subsequent IL-2 infusion and that the combination of anti-CD3 followed by IL-2 did not improve upon the antitumor activity previously seen with IL-2 alone.

Original languageEnglish (US)
Pages (from-to)481-491
Number of pages11
JournalClinical Cancer Research
Volume1
Issue number5
StatePublished - May 1 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hank, J. A., Albertini, M., Wesly, O. H., Schiller, J. H., Borchert, A., Moore, K., Bechhofer, R., Storer, B., Gan, J., Gambacorti, C., Sosman, J., & Sondel, P. M. (1995). Clinical and Immunological Effects of Treatment with Murine Anti-Cd3 Monoclonal Antibody Along with Interleukin 2 in Patients with Cancer. Clinical Cancer Research, 1(5), 481-491.