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

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-3lg), which has been shown to act as an adjuvant for priming T helper type 1 and cytotoxicT-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-3lg was administered s.c. at the immunotherapy site. Results: The studies reported here show that combining LAG-3lg 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 IFNγ-secreting CD8 + Tcells and a significantly increased infiltration of activated effector CD8+ Tcells into the tumor. Moreover, an increase in antigen-specific lgG1 humoral responses was detected in serum of animals injected with the combination therapy compared with animals injected with either therapy alone. Conclusion: LAG-3lg 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. © 2008 American Association for Cancer Research.