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Lymphocyte Activation Gene-3 Fusion Protein Increases the Potency of a Granulocyte Macrophage Colony-Stimulating Factor–Secreting Tumor Cell Immunotherapy

Authors' Affiliations: ¹ Cell Genesys, Inc., South San Francisco, California and ² Immutep S.A., Paris, France

Requests for reprints: Betty Li, Cell Genesys, Inc., 500 Forbes Boulevard, South San Francisco, CA 94080. Phone: 650-266-2962; Fax: 650-266-3080; E-mail: betty.li{at}cellgenesys.com.

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-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.