Measles virus selectively blind to SLAM has oncolytic efficacy against nectin-4-expressing pancreatic cancer cells

Summary

Pancreatic cancer is one of the most intractable cancers and has a devastating prognosis over the past three decades the 5-year survival rate has been less than 10%. Therefore, development of a novel anticancer treatment for pancreatic cancer is a matter of urgency. We previously developed an oncolytic recombinant measles virus (MV), rMV-SLAMblind, which had lost the ability to bind to its principal receptor, signaling lymphocyte activity molecule (SLAM), but which selectively infected and efficiently killed nectin-4-expressing breast and lung cancer cells. In this study, we analyzed the antitumor effect of this virus against pancreatic cancer. Nectin-4 was expressed on the surface of 4/16 tested pancreatic cancer cell lines, which were efficiently infected and killed by rMV-SLAMblind in vitro. The intratumoral inoculation of rMV-SLAMblind suppressed the growth of KLM1 and Capan-2 cells xenografted in SCID mice. The sequence analysis of MV isolated from the tumor revealed that the designed mutation in the H protein of rMV-SLAMblind had been stably maintained for 47 days after the last inoculation. These results suggest that rMV-SLAMblind is a promising candidate for the novel treatment of pancreatic cancer.

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