Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF.
Mol Ther
; 14(3): 361-70, 2006 Sep.
Article
in En
| MEDLINE
| ID: mdl-16905462
ABSTRACT
Targeted oncolytic viruses and immunostimulatory therapeutics are being developed as novel cancer treatment platforms. These approaches can be combined through the expression of immunostimulatory cytokines from targeted viruses, including adenoviruses and herpesviruses. Although intratumoral injection of such viruses has been associated with tumor growth inhibition, eradication of distant metastases was not reported. The major limitations for this approach to date have been (1) inefficient intravenous virus delivery to tumors and (2) the lack of predictive, immunocompetent preclinical models. To overcome these hurdles, we developed JX-594, a targeted, thymidine kinase(-) vaccinia virus expressing human GM-CSF (hGM-CSF), for intravenous (i.v.) delivery. We evaluated two immunocompetent liver tumor models a rabbit model with reproducible, time-dependent metastases to the lungs and a carcinogen-induced rat liver cancer model. Intravenous JX-594 was well tolerated and had highly significant efficacy, including complete responses, against intrahepatic primary tumors in both models. In addition, whereas lung metastases developed in all control rabbits, none of the i.v. JX-594-treated rabbits developed detectable metastases. Tumor-specific virus replication and gene expression, systemically detectable levels of hGM-CSF, and tumor-infiltrating CTLs were also demonstrated. JX-594 holds promise as an i.v.-delivered, targeted virotherapeutic. These two tumor models hold promise for the optimization of this approach.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vaccinia virus
/
Granulocyte-Macrophage Colony-Stimulating Factor
/
Oncolytic Virotherapy
/
Liver Neoplasms
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mol Ther
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2006
Document type:
Article
Affiliation country:
Corea del Sur