Production and characterization of a bicistronic Moloney-based retroviral vector expressing human interleukin 2 and herpes simplex virus thymidine kinase for gene therapy of cancer.
Gene Ther
; 5(7): 1003-7, 1998 Jul.
Article
en En
| MEDLINE
| ID: mdl-9813672
Gene-based therapeutic strategies for cancer mainly include augmentation of immunotherapeutic and chemotherapeutic approaches. In this study we report the design and functional assay of a novel bicistronic Moloney-based retroviral vector expressing human interleukin-2 (IL-2) and herpesvirus thymidine kinase (tk) through a cap-dependent translation and an internal ribosome entry site (IRES)-regulated translation, respectively. This construct has the potential for allowing combination of cytokine and suicide gene therapy, especially in areas such as the brain, composed of post-mitotic cells refractory to transduction by type C retroviral vectors. Accordingly, human glioma cells were used as targets for gene transfer after selecting a packaging cell clone that produced a reasonable titer of recombinant virus and expressed high levels of IL-2 and tk transcripts. Although transduction efficiency was reduced in glioma cells as compared with murine NIH 3T3 cells, transgene expression was effectively achieved. Transduced glioma cells were sensitive to ganciclovir and secreted around 1000 U/ml IL-2 in the culture supernatants. Simultaneous production of IL-2 and tk in vivo by genetically treated tumor cells would hopefully potentiate the effect of gangiclovir-induced metabolic suicide, possibly by boosting the immune response associated with tumor debulking or by amplifying the bystander response.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timidina Quinasa
/
Terapia Genética
/
Ingeniería Genética
/
Interleucina-2
/
Vectores Genéticos
/
Virus del Sarcoma Murino de Moloney
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Reino Unido