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, John Edward Janik

Research output: Contribution to journalArticle

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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 - Jan 1 1992

Fingerprint

Monoclonal Antibodies
Neoplasms
Therapeutics
Interleukin-2 Receptors
Headache
Cerebrospinal Fluid
CD27 Antigens
Lymphocytes
T-Lymphocytes
Lymphocytosis
Spinal Puncture
Maximum Tolerated Dose
Fibrosarcoma
Signs and Symptoms
Anti-Idiotypic Antibodies
Interleukin-6
Clone Cells
Pressure
Growth
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors : A Phase IA/B Study. / Urba, Walter J.; Ewel, Cynthia; Kopp, William; Rossio, Jeffrey; Beveridge, Joy; Fenton, Robert; Janik, John; Longo, Dan L.; Janik, John Edward.

In: Cancer Research, Vol. 52, No. 9, 01.01.1992, p. 2394-2401.

Research output: Contribution to journalArticle

Urba, WJ, Ewel, C, Kopp, W, Rossio, J, Beveridge, J, Fenton, R, Janik, J, Longo, DL & Janik, JE 1992, 'Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors: A Phase IA/B Study', Cancer Research, vol. 52, no. 9, pp. 2394-2401.
Urba WJ, Ewel C, Kopp W, Rossio J, Beveridge J, Fenton R et al. Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors: A Phase IA/B Study. Cancer Research. 1992 Jan 1;52(9):2394-2401.
Urba, Walter J. ; Ewel, Cynthia ; Kopp, William ; Rossio, Jeffrey ; Beveridge, Joy ; Fenton, Robert ; Janik, John ; Longo, Dan L. ; Janik, John Edward. / Anti-CD3 Monoclonal Antibody Treatment of Patients with CD3-Negative Tumors : A Phase IA/B Study. In: Cancer Research. 1992 ; Vol. 52, No. 9. pp. 2394-2401.
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