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


METHODS
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.


CONCLUSIONS
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.
Cell Genesys, Inc., 500 Forbes Boulevard, South San Francisco, CA 94080, USA. betty.li@cellgenesys.com
Betty
B
Li
Melinda
M
VanRoey
Frederic
F
Triebel
Karin
K
Jooss
D000818:Animals; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; D016173:Macrophage Colony-Stimulating Factor; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse