Immunomodulatory function of interferon-gamma in patients with metastatic melanoma

Results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987

John M. Kirkwood, John Bryant, Joan H. Schiller, Martin M. Oken, Ernest C. Borden, Theresa L. Whiteside

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Interferon-gamma (IFN-γ) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-γ in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-γ (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-γ therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses ≤0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN- γ reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-γ has been shown to have significant effects on the T-cell compartment of the immune system.

Original languageEnglish (US)
Pages (from-to)146-157
Number of pages12
JournalJournal of Immunotherapy
Volume20
Issue number2
StatePublished - 1997

Fingerprint

Interferon-gamma
Melanoma
Natural Killer Cells
T-Lymphocytes
CD4-CD8 Ratio
San Francisco
Interferons
Monocytes
Immune System
Clinical Trials
Lymphocytes
Phenotype
Therapeutics
Population

Keywords

  • ECOG study
  • IFN-γ
  • Immunomodulation
  • Metastatic melanoma
  • Phase II-B

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Immunomodulatory function of interferon-gamma in patients with metastatic melanoma : Results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987. / Kirkwood, John M.; Bryant, John; Schiller, Joan H.; Oken, Martin M.; Borden, Ernest C.; Whiteside, Theresa L.

In: Journal of Immunotherapy, Vol. 20, No. 2, 1997, p. 146-157.

Research output: Contribution to journalArticle

Kirkwood, John M. ; Bryant, John ; Schiller, Joan H. ; Oken, Martin M. ; Borden, Ernest C. ; Whiteside, Theresa L. / Immunomodulatory function of interferon-gamma in patients with metastatic melanoma : Results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987. In: Journal of Immunotherapy. 1997 ; Vol. 20, No. 2. pp. 146-157.
@article{1c5a531e7ee84481a124562cd0434091,
title = "Immunomodulatory function of interferon-gamma in patients with metastatic melanoma: Results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987",
abstract = "Interferon-gamma (IFN-γ) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-γ in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-γ (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-γ therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+{\%} p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses ≤0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN- γ reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-γ has been shown to have significant effects on the T-cell compartment of the immune system.",
keywords = "ECOG study, IFN-γ, Immunomodulation, Metastatic melanoma, Phase II-B",
author = "Kirkwood, {John M.} and John Bryant and Schiller, {Joan H.} and Oken, {Martin M.} and Borden, {Ernest C.} and Whiteside, {Theresa L.}",
year = "1997",
language = "English (US)",
volume = "20",
pages = "146--157",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Immunomodulatory function of interferon-gamma in patients with metastatic melanoma

T2 - Results of a phase II-B trial in subjects with metastatic melanoma, ECOG study E 4987

AU - Kirkwood, John M.

AU - Bryant, John

AU - Schiller, Joan H.

AU - Oken, Martin M.

AU - Borden, Ernest C.

AU - Whiteside, Theresa L.

PY - 1997

Y1 - 1997

N2 - Interferon-gamma (IFN-γ) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-γ in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-γ (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-γ therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses ≤0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN- γ reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-γ has been shown to have significant effects on the T-cell compartment of the immune system.

AB - Interferon-gamma (IFN-γ) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-γ in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-γ (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-γ therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses ≤0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN- γ reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-γ has been shown to have significant effects on the T-cell compartment of the immune system.

KW - ECOG study

KW - IFN-γ

KW - Immunomodulation

KW - Metastatic melanoma

KW - Phase II-B

UR - http://www.scopus.com/inward/record.url?scp=0031436375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031436375&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 146

EP - 157

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 2

ER -