Bacillus Calmette-Guérin plus interleukin-2 and/or granulocyte/macrophage-colony-stimulating factor enhances immunocompetent cell production of interferon-γ, which inhibits B16F10 melanoma cell growth in vitro

Toshihiro Fujimoto; Michael A. O'Donnell; Akos Szilvasi; Hua Yang; Rosemary B Duda

doi:10.1007/s002620050283

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Bacillus Calmette-Guérin plus interleukin-2 and/or granulocyte/macrophage-colony-stimulating factor enhances immunocompetent cell production of interferon-γ, which inhibits B16F10 melanoma cell growth in vitro

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Bacillus Calmette-Guérin plus interleukin-2 and/or granulocyte/macrophage-colony-stimulating factor enhances immunocompetent cell production of interferon-γ, which inhibits B16F10 melanoma cell growth in vitro

Toshihiro Fujimoto, Michael A. O'Donnell, Akos Szilvasi, Hua Yang and Rosemary B Duda

Cancer Immunology, Immunotherapy, Vol.42(5), pp.280-284

07/24/1996

DOI: 10.1007/s002620050283

PMCID: PMC11037850

PMID: 8706049

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Abstract

Although immunotherapy with bacillus Calmette Guérin (BCG) is an established adjuvant treatment for malignant melanoma, the mechanism of its role in this process is unclear. To investigate the possible contribution of tumor-inhibitory cytokines induced by BCG, B16F10 melanoma cell growth in culture was assessed in response to purified cytokines and conditioned media of BCG-stimulated splenocytes. Interferon-γ (IFNγ) was the most potent single agent (IC50≈50 pg/ml). Tumor necrosis factor α was substantially weaker (IC50>10 ng/ml) but provided synergy with IFNγ. None of the other cytokines such as interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12, or granulocyte/macrophage-colony-stimulating factor had direct antitumor activity against B16F10 melanoma cells. However, when IL-2 and/or GM-CSF were combined with BCG either by exogenous addition or through endogenous production by novel cytokine-secreting recombinant BCG (rBCG), a substantial increase in INFγ production by splenocytes was observed. Antitumor activity of this conditioned medium directly correlated with IFNγ concentration and was completely blocked by neutralizing antibody to IFNγ. These results suggest that BCG may exert part of its antitumor action on melanoma through the induction of IFNγ, which can be greatly enhanced through the concomitant addition of IL-2 and/or GM-CSF. Furthermore, by utilizing rBCG that secrete these cytokines, it may be possible to potentiate the antitumor effect of BCG directly at the site of BCG inoculation.

Details

Title: Subtitle: Bacillus Calmette-Guérin plus interleukin-2 and/or granulocyte/macrophage-colony-stimulating factor enhances immunocompetent cell production of interferon-γ, which inhibits B16F10 melanoma cell growth in vitro
Creators: Toshihiro Fujimoto - Beth Israel Deaconess Hospital
Michael A. O'Donnell
Akos Szilvasi - Harvard Medical School
Hua Yang - Harvard Medical School
Rosemary B Duda - Harvard Medical School
Resource Type: Journal article
Publication Details: Cancer Immunology, Immunotherapy, Vol.42(5), pp.280-284
DOI: 10.1007/s002620050283
PMID: 8706049
PMCID: PMC11037850
NLM abbreviation: Cancer Immunol Immunother
ISSN: 0340-7004
eISSN: 1432-0851
Language: English
Date published: 07/24/1996
Academic Unit: Urology
Record Identifier: 9984319971702771

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