A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model.
Cell Biol Int
; 45(6): 1202-1210, 2021 Jun.
Article
en En
| MEDLINE
| ID: mdl-33501754
ABSTRACT
Oncolytic viruses (OV) have shown excellent safety and efficacy in preclinical and clinical studies. Influenza A virus (IAV) is considered a promising oncolytic virus. In this report, we generated a recombinant influenza virus expressing an immune checkpoint blockade agent targeting CTLA4. Using reverse genetics, a recombinant influenza virus, termed rFlu-CTLA4, encoding the heavy chain of a CTLA4 antibody on the PB1 segment and the light chain of the CTLA4 antibody on the PA segment was produced. RFlu-CTLA4 could replicate to high titers, and antibodies were produced in the allantoic fluid of infected eggs. Furthermore, the selective cytotoxicity of the virus was higher in various hepatocellular carcinoma cancer cell lines than in the normal cell line L02 in vitro, as indicated by MTS assays. More importantly, in a subcutaneous H22 mouse hepatocarcinoma model, intratumoral injections of rFlu-CTLA4 inhibited the growth of treated tumors and increased the overall survival of mice compared with injections of the PR8 virus. Taken together, these results warrant further exploration of this novel recombinant influenza virus for its potential use as a single or combination agent for cancer immunotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus de la Influenza A
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Virus Oncolíticos
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Viroterapia Oncolítica
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Antígeno CTLA-4
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Inmunoterapia
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Neoplasias
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Biol Int
Año:
2021
Tipo del documento:
Article
País de afiliación:
China