Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors: A Phase IA/B Study

Walter J. Urba, Cynthia Ewel, William Kopp, Jeffrey Rossio, Joy Beveridge, Robert Fenton, John Janik, Dan L. Longo, Mario Sznol

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20 Scopus citations

Abstract

Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1,10,30, and 100 meg/patient. Five other patients received anti-CD3 at 30 meg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 meg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 meg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3,8 of 16 patients tested developed human anti-mouse antibodies.

Original languageEnglish (US)
Pages (from-to)2394-2401
Number of pages8
JournalCancer Research
Volume52
Issue number9
StatePublished - May 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Urba, W. J., Ewel, C., Kopp, W., Rossio, J., Beveridge, J., Fenton, R., Janik, J., Longo, D. L., & Sznol, M. (1992). Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors: A Phase IA/B Study. Cancer Research, 52(9), 2394-2401.