Immune response elicited in the tumor microenvironment upon rMV-SLAMblind cancer virotherapy.
Cancer Sci
; 114(5): 2158-2168, 2023 May.
Article
em En
| MEDLINE
| ID: mdl-36715555
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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Base de dados:
MEDLINE
Assunto principal:
Vírus Oncolíticos
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Terapia Viral Oncolítica
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article