Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer

J. A. Hank, M. Albertini, O. H. Wesly, J. H. Schiller, A. Borchert, K. Moore, R. Bechhofer, B. Storer, J. Gan, C. Gambacorti, J. Sosman, P. M. Sondel

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Abstract

Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients wth 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 μg/m2 anti-CD3. One patient received 3000 μg/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, pentoxifyIline 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 μg/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 ill 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 - 1995

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Interleukin-2
Monoclonal Antibodies
Neoplasms
Pentoxifylline
Therapeutics
Tumor Necrosis Factor-alpha
Hypotension
Serum
T-Lymphocytes
Interleukin-2 Receptors
Blood Urea Nitrogen
Lymphocyte Count
Bilirubin
Dyspnea
Creatinine
Cytokines
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hank, J. A., Albertini, M., Wesly, O. H., Schiller, J. H., Borchert, A., Moore, K., ... 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.

Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer. / 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.

In: Clinical Cancer Research, Vol. 1, No. 5, 1995, p. 481-491.

Research output: Contribution to journalArticle

Hank, JA, Albertini, M, Wesly, OH, Schiller, JH, Borchert, A, Moore, K, Bechhofer, R, Storer, B, Gan, J, Gambacorti, C, Sosman, J & Sondel, PM 1995, 'Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer', Clinical Cancer Research, vol. 1, no. 5, pp. 481-491.
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. / Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 5. pp. 481-491.
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