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Clin Cancer Res. 2008 Jun 1;14(11):3545-54. doi: 10.1158/1078-0432.CCR-07-5200.

Lymphocyte activation gene-3 fusion protein increases the potency of a granulocyte macrophage colony-stimulating factor-secreting tumor cell immunotherapy.

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  • 1Cell Genesys, Inc., 500 Forbes Boulevard, South San Francisco, CA 94080, USA. betty.li@cellgenesys.com

Abstract

PURPOSE:

The purpose of the present study was to evaluate granulocyte macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell immunotherapy, which is known to stimulate a potent and long-lasting antigen-specific immune response in combination with lymphocyte activation gene-3 fusion protein (LAG-3Ig), which has been shown to act as an adjuvant for priming T helper type 1 and cytotoxic T-cell responses.

EXPERIMENTAL DESIGN:

Survival and immune monitoring studies were done in the B16 melanoma model. GM-CSF-secreting tumor cell immunotherapy was administered as a single s.c. injection and LAG-3Ig was administered s.c. at the immunotherapy site.

RESULTS:

The studies reported here show that combining LAG-3Ig with GM-CSF-secreting tumor cell immunotherapy prolonged the survival of tumor-bearing animals compared with animals treated with either therapy alone. Prolonged survival correlated with increased numbers of systemic IFN gamma-secreting CD8+ T cells and a significantly increased infiltration of activated effector CD8+ T cells into the tumor. Moreover, an increase in antigen-specific IgG1 humoral responses was detected in serum of animals injected with the combination therapy compared with animals injected with either therapy alone.

CONCLUSION:

LAG-3Ig combined with a GM-CSF-secreting tumor cell immunotherapy stimulated both cellular and humoral antitumor immune responses that correlated with prolonged survival in tumor-bearing animals.

PMID:
18519788
DOI:
10.1158/1078-0432.CCR-07-5200
[PubMed - indexed for MEDLINE]
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