title: Measles virus selectively blind to signaling lymphocyte activity molecule has oncolytic efficacy against nectin-4-expressing pancreatic cancer cells.
abstract: 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 <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, that 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.
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Mutsumi
authors: M
authors: Awano
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Tomoko
authors: T
authors: Fujiyuki
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Koichiro
authors: K
authors: Shoji
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Yosuke
authors: Y
authors: Amagai
authors: Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Yoshinori
authors: Y
authors: Murakami
authors: Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Yoichi
authors: Y
authors: Furukawa
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Sato
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Misako
authors: M
authors: Yoneda
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Chieko
authors: C
authors: Kai
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008459:Measles virus / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D000075983:Nectins
chemical_list: D015815:Cell Adhesion Molecules; C442228:NECTIN4 protein, human; D000075983:Nectins
keywords: Measles virus; nectin-4/PVRL4; oncolytic virus therapy; pancreatic cancer; xenograft