An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I.
J Clin Invest
; 134(15)2024 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-38861331
ABSTRACT
Viral vectors are being used for the treatment of cancer. Yet, their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this vector results in improved tumor control and survival. Importantly, r3LCMV improved tumor control in immunodeficient Rag1-/- mice and MyD88-/- mice, suggesting that multiple pathways contributed to the antitumoral effects. The antitumoral effects of r3LCMV were also observed when this vector was administered several weeks before tumor challenges, suggesting the induction of trained immunity. Single-cell RNA sequencing analyses, antibody blockade experiments, and knockout models revealed a critical role for host-intrinsic IFN-I in the antitumoral efficacy of r3LCMV vectors. Collectively, these data demonstrate potent antitumoral effects by r3LCMV vectors and unveil multiple mechanisms underlying their antitumoral efficacy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
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Camundongos Knockout
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Vetores Genéticos
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Vírus da Coriomeningite Linfocítica
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Clin Invest
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J. clin. invest
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Journal of clinical investigation
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
Estados Unidos