Generation of Immuno-Modulator Receptors (IMR)-transduced human JY cell lines to test combo immuno-therapies.

Abstract T cell activation is initiated by signal 1 through an antigen–specific TCR recognition and engagement, then a second co-stimulation signal is needed. This co-stimulation is provided by the interaction of IMR receptors and ligands expressed on the T cells and APC or tumor cells. These receptor-ligand interactions can either stimulate or inhibit T cell activation and they are the main targets for the new therapeutics developed in the oncology field. The establishment of Ag-specific human T cell clones is essential to study IMR biology and even more to test different biologics targeting those molecules. In our laboratory, we developed primary-cell based assays to test such biologics. In those assays allo-Ag-specific human CD4+ T cell clones are activated by HLA-DR-positive JY cells, a human B cell line, to proliferate and to produce IFNγ. To analyze the efficacy of PD-1/Lag3 and PD-1/TIGIT biologics, we generated by lentivirus transduction, different JY cell line clones expressing PD-L1, CD155 or PD-L1/CD155. The JY clones isolated after infection showed a stable expression of the IMRs and they modulated activation of the CD4+ T cell clones.