Soluble Human LAG-3 Molecule Amplifies theIn vitroGeneration of Type 1 Tumor-Specific Immunity

Chiara Casati, Chiara Camisaschi, Francesca Rini, Flavio Arienti, Licia Rivoltini, Frédéric Triebel, Giorgio Parmiani, Chiara Castelli
2006 Cancer Research  
The adjuvant activities of the human lymphocyte activation gene-3 (LAG-3) molecule have been evaluated in a human setting by investigating the ability of a soluble recombinant human LAG-3 protein (hLAG-3Ig) to enhance the in vitro induction of viral-and tumor-specific CTLs. We found that soluble human LAG-3 significantly sustained the generation and expansion of influenza matrix protein Melan-A/MART-1 and survivin-specific CD8 + T lymphocytes in peripheral blood mononuclear cells (PBMC) of both
more » ... cancer patients and healthy donors, showing its ability to boost CD8 + T-cell memory response or to prime naive T cells in vitro. The peptide-specific T cells generated in the presence of hLAG-3Ig were endowed with cytotoxic activity and enhanced release of type 1 cytotoxic T (Tc1) cytokines and were able to recognize tumor cells expressing their nominal antigen. Phenotype and cytokine/chemokines produced by antigen-presenting cells (APC) of PBMCs exposed in vitro for 2 days to peptide and hLAG-3Ig indicate that the LAG-3-mediated adjuvant effect may depend on a direct activation of circulating APCs. Our data revealed the activity of hLAG-3Ig in inducing tumorassociated, antigen-specific CD8 + T-cell responses in a human setting and strongly support the conclusion that this recombinant protein is a potential candidate adjuvant for cancer vaccines. (Cancer Res 2006; 66(8): 4450-60)
doi:10.1158/0008-5472.can-05-2728 pmid:16618772 fatcat:7go26k6225aepltfakucirvebm