Oral Presentation International Veterinary Immunology Symposium 2016

Immunocompetent animal model to examine influence of immunity on oncolytic virotherapy with a recombinant measles virus (#31)

Koichiro Shoji 1 , Tomoko Fujiyuki 1 , Yosuke Amagai 1 , Hiroki Sato 1 , Misako Yoneda 1 , Chieko Kai 1
  1. Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Oncolytic virotherapy is expected to become a novel and efficient strategy for cancer treatment. Previously we generated a recombinant measles virus (rMV-SLAMblind) that selectively uses Nectin-4 as its receptor, which is up-regulated in tumor cells. The virus infected and killed human cancer cells. We recently found that it could also use dog Nectin-4, and thus infected canine mammary cancer (CMC) cells expressing Nectin-4. In addition, the administration of rMV-SLAMblind greatly suppressed the progression of tumors in SCID mice xenografted with a CMC cell line. Thus rMV-SLAMblind is expectedly promising as a novel strategy for cancer treatment not only of human but also of dog cancer patients.

It is well known that MV induces strong cellular immunity, similarly to canine distemper virus and rinderpest virus of the same genus as MV, morbillivirus. Therefore it is expected that administration of rMV-SLAMblind to animals possessing immunity against MV will rapidly induce cellular immunity against the virus infected tumor cells by a boost effects, which may enhance therapeutic effects of rMV-SLAMblind. An animal model using immunocompetent mice should be an ideal model to examine synergistic influence of host immunity. To develop such a model, we established a stable cell line of mouse tumor cells (E.G7) expressing Nectin-4. The subcutaneously transplanted cells to C57BL/6 mice successfully grew and formed tumors. In addition, intratumoral administration of rMV-SLAMblind significantly suppressed the tumor progression, and half of the mice showed complete regression. These results suggest that this mouse model should be useful to examine influence of immunity on rMV-SLAMblind therapy. Induction of cellular immunity, influence of MV vaccination, and its contribution to rMV-SLAMblind therapy using the model are currently under investigation.