Immune response elicited in the tumor microenvironment upon rMV‐SLAMblind cancer virotherapy

• Published in: Cancer science 2023-05, Vol.114 (5), p.2158-2168
• Main Authors: Moritoh, Kanako, Shoji, Koichiro, Amagai, Yosuke, Fujiyuki, Tomoko, Sato, Hiroki, Yoneda, Misako, Kai, Chieko
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antitumor activity; antitumor immune response; Cancer; Cancer therapies; CD8 antigen; Cell activation; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cloning; Flow cytometry; Humans; Immunity; Immunocompetence; immunocompetent mouse model; Immunodeficiency; Immunotherapy; Infections; Laboratories; Lymphocytes; Lymphocytes T; Measles; Melanoma; Mice; Natural killer cells; NECTIN4; Neoplasms - therapy; Oncolysis; Oncolytic Virotherapy; Oncolytic Viruses - physiology; Original; ORIGINAL ARTICLES; Penicillin; rMV‐SLAMblind; Transplantation; Tumor cell lines; Tumor cells; Tumor Microenvironment; Tumors; Viral infections; Viruses
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15740

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. We generated an immunocompetent mouse model to study our oncolytic virus, designated as rMV‐SLAMblind. We evaluated the induction of immune responses after rMV‐SLAMblind cancer therapy with this model.