Immune response elicited in the tumor microenvironment upon rMV-SLAMblind cancer virotherapy |
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Authors: | Kanako Moritoh Koichiro Shoji Yosuke Amagai Tomoko Fujiyuki Hiroki Sato Misako Yoneda Chieko Kai |
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Affiliation: | Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan |
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Abstract: | Oncolytic virotherapy is a promising therapy for cancer. We previously established a recombinant measles virus (rMV-SLAMblind) that targets NECTIN4-expressing cancer cells and demonstrated its antitumor effects using a xenograft model in an immunodeficient mouse. In the current study, to investigate the immune response after rMV-SLAMblind therapy, we developed an immunocompetent cancer mouse model by introducing the NECTIN4 gene into mouse cancer cell lines. NECTIN4-expressing mouse cancer cells were successfully killed by rMV-SLAMblind in vitro. After transplantation of the NECTIN4-expressing tumor cells, rMV-SLAMblind significantly suppressed tumor growth in immunocompetent mice. Thus, this immunocompetent mouse cancer model could be a powerful tool in which to study the effect of rMV-SLAMblind therapy on the immune response. Using this model we found that rMV-SLAMblind elicited significant activation of natural killer cells, type 1 helper T cells and the tumor-specific CD8+ T-cell response in the tumor microenvironment. Immune cell depletion study revealed that CD8+ cells particularly played significant roles in the therapeutic efficacy of rMV-SLAMblind. Thus, rMV-SLAMblind exerts a therapeutic effect, not only directly by tumor cell killing, but also indirectly by efficient induction of antitumor immunity. |
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Keywords: | antitumor immune response immunocompetent mouse model NECTIN4 oncolytic virotherapy rMV-SLAMblind |
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