Elucidating mechanisms of a non-replicating virotherapy to induce anti-tumor effects

HVJ-E is an UV-irradiated Sendai virus that mostly lost replicating ability. Recently, HVJ-E has been shown to have anti-tumor effects both in mouse tumor model and in human with malignant tumors. However, how HVJ-E induces tumor regression is still enigmatic. Here, we show a phase I data of HVJ-E in patients with cutaneous malignant melanoma and molecular mechanisms of HVJ-E-induced repression of tumor growth through apolipoproteins expression in cancerous cells in vivo. HVJ-E represses tumor growth in dose dependent manner in human without any significant severe adverse effects. HVJ-E also shows significant tumor regression activity in melanoma patient-derived xenograft model as well as several tumor model mice, including breast cancer, colon carcinoma, prostate cancer, and melanoma. While the anti-tumor effects by HVJ-E does not require lymphocytes, they require changes in gene expression in cancer cells in vivo, through the infection to the target cancer cells since HVJ-E-infection resistant cell, LL/2, shows no response to the HVJ-E intratumor injection.