Expression of nectin-1 and HVEM by tumor cells predicts sensitivity to herpes oncolytic therapy

3370 Attenuated, oncolytic herpes simplex viruses (HSV) can infect and lyse a variety of malignant tumor cell lines. However, the determinants of tumor sensitivity to oncolytic HSV remain poorly understood. For successful infection of a tumor cell to occur, HSV-1 must attach and fuse with the cell membrane through one of three receptors (nectin-1, HVEM, 3-OST). We hypothesized that the level of receptor expression by tumor cells is a determinant of sensitivity to HSV entry and oncolysis. A panel of eight head and neck (1386, MSK922, 1986, SCC15, SCC25, HN686, MSKQLL1, MSKQLL2) and lung (H322, 2030, A157, H1299) carcinoma lines were studied. The CHOK1 cell line does not express nectin-1 or HVEM, and was used as a control. The expression of cell surface nectin-1 and HVEM receptors was measured by quantitative FACS using monoclonal fluorescent antibodies. Two parameters were measured: the average number of antibody binding sites per cell (ABS) and overall percentage of positive cells (PPC). An attenuated, oncolytic HSV (NV1023) expressing lacZ was used to determine sensitivity to HSV entry and cytotoxicity for each cell line. Viral entry was measured by lacZ assay (MOI 5, 12 hrs). Cytotoxicity was measured by lactate dehydrogenase assay (MOI 0.1, 72 hrs). Correlations as determined by Pearson’s coefficient between nectin-1 ABS and viral entry (0.52) or cytotoxicity (0.56) were both significant (p