Immunomodulation of interleukin-2 by cyclophosphamide: A phase ib trial

Jeffrey S. Abrams, Julie L. Eiseman, Teresa J. Melink, Raji Sridhara, Deborah J. Hiponia, Melanie M. Bell, Chandra Belani, Joseph Aisner

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The objective of this phase IB trail was to determine if cyclophosphamide (CY) could enhance the immune effects of interleukin-2 (IL-2), and if it could, was there an optimal immunomodulatory dosage. IL-2 alone at 30 million IU/m2 thrice weekly for 6 weeks or in combination with varying dosages of CY (300, 600, and 1,200 mg/m2) administered 3 days before IL-2 and repeated 3 weeks later was given to consecutive cohorts of patients (at least five per group) with advanced malignancies of varying types. To gauge the immune effects of the treatment, the variation in the amount of lymphokine-activated killer (LAK) cells generated in the peripheral blood mononuclear cells of patients and in a control group of normal volunteers was measured weekly over 7 consecutive weeks. Other immune parameters [natural killer cells (NK), peripheral blood eosinophils and lymphocytes, cell surface markers, soluble IL-2 receptor, and IL-2 antibodies] were also closely followed to study if they correlated with the degree of LAK activity. The group of patients that received low-dosage CY (300 mg/m2) and IL-2 produced the highest and most sustained levels of LAK and NK activity (p < 0.05) when compared with the cohorts receiving IL-2 alone or to those receiving the higher dosages of CY. No other immune parameter showed a significant difference between the groups. Although low-dosage CY does increase the LAK activity seen with IL-2, only randomized clinical trials can determine if this enhancement will improve tumor responses.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalJournal of Immunotherapy
Volume14
Issue number1
DOIs
StatePublished - Jan 1 1993

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Immunomodulation
Cyclophosphamide
Interleukin-2
Lymphokines
Natural Killer Cells
Lymphokine-Activated Killer Cells
Interleukin-2 Receptors
Eosinophils
Blood Cells
Neoplasms
Healthy Volunteers
Randomized Controlled Trials
Lymphocytes
Control Groups
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Abrams, J. S., Eiseman, J. L., Melink, T. J., Sridhara, R., Hiponia, D. J., Bell, M. M., ... Aisner, J. (1993). Immunomodulation of interleukin-2 by cyclophosphamide: A phase ib trial. Journal of Immunotherapy, 14(1), 56-64. https://doi.org/10.1097/00002371-199307000-00008
Abrams, Jeffrey S. ; Eiseman, Julie L. ; Melink, Teresa J. ; Sridhara, Raji ; Hiponia, Deborah J. ; Bell, Melanie M. ; Belani, Chandra ; Aisner, Joseph. / Immunomodulation of interleukin-2 by cyclophosphamide : A phase ib trial. In: Journal of Immunotherapy. 1993 ; Vol. 14, No. 1. pp. 56-64.
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Abrams, JS, Eiseman, JL, Melink, TJ, Sridhara, R, Hiponia, DJ, Bell, MM, Belani, C & Aisner, J 1993, 'Immunomodulation of interleukin-2 by cyclophosphamide: A phase ib trial', Journal of Immunotherapy, vol. 14, no. 1, pp. 56-64. https://doi.org/10.1097/00002371-199307000-00008

Immunomodulation of interleukin-2 by cyclophosphamide : A phase ib trial. / Abrams, Jeffrey S.; Eiseman, Julie L.; Melink, Teresa J.; Sridhara, Raji; Hiponia, Deborah J.; Bell, Melanie M.; Belani, Chandra; Aisner, Joseph.

In: Journal of Immunotherapy, Vol. 14, No. 1, 01.01.1993, p. 56-64.

Research output: Contribution to journalArticle

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Abrams JS, Eiseman JL, Melink TJ, Sridhara R, Hiponia DJ, Bell MM et al. Immunomodulation of interleukin-2 by cyclophosphamide: A phase ib trial. Journal of Immunotherapy. 1993 Jan 1;14(1):56-64. https://doi.org/10.1097/00002371-199307000-00008