Combination of viral oncolysis and tumor-specific immunity to control established tumors.
OBJECTIVE
Advanced-stage cancers are extremely difficult to treat and rarely result in a cure. The application of oncolytic viruses is a potential strategy for controlling advanced-stage cancer because intratumoral (i.t.) injection of an oncolytic virus, such as vaccinia virus, results in tumor cell lysis and subsequent release of tumor antigens into the microenvironment. Furthermore, the viruses can serve as a vehicle for delivering genes of interest to cancer cells.


METHODS
In the current study, we hypothesize that in tumor-bearing mice primed with DNA encoding an immunogenic foreign antigen, ovalbumin (OVA) followed by a boost with i.t. administration of vaccinia virus encoding the same foreign antigen, OVA, can generate enhanced antitumor effects through the combination of viral oncolysis and tumor-specific immunity.


RESULTS
We observed that tumor-bearing mice primed with OVA DNA and boosted with vaccinia encoding OVA (Vac-OVA) generated significant therapeutic antitumor effects as well as induced significant levels of OVA-specific CD8+ T cells in two different tumor models. Furthermore, treatment with Vac-OVA not only kills the tumor and stromal cells directly but also renders the tumor cells and surrounding stromal cells susceptible to OVA-specific CD8+ T-cell killing, resulting in enhanced antitumor therapeutic effects.


CONCLUSIONS
Thus, the current study may provide a novel therapeutic strategy for the control of advanced-stage cancers.
Chuang
Chi-Mu
CM
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Monie
Archana
A
Wu
Annie
A
Pai
Sara I
SI
Hung
Chien-Fu
CF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D007371:Interferon-gamma; D010047:Ovalbumin