Immune-mediated anti-neoplastic effect of intratumoral RSV envelope glycoprotein expression is related to apoptotic death of tumor cells but not to the size of syncytia.
OBJECTIVE
To promote the development of improved tumor vaccination strategies relying on the intratumoral expression of viral fusogenic membrane proteins, we elucidated whether the size of syncytia or the way tumor cells die has an effect on the therapeutic outcome.


METHODS
In two syngeneic subcutaneous murine colon cancer models we assessed the anti-neoplastic effect on vector-treated and contralateral untreated tumors.


RESULTS
Intratumoral injection of a replication-defective adenovirus encoding respiratory syncytial virus fusion protein (RSV-F) alone (Ad.RSV-F) or together with the attachment glycoprotein RSV-G (Ad.RSV-F/G) led to a significant growth reduction of the vector-treated and contralateral untreated tumors. The treatment response was associated with a strong tumor-specific CTL response and significantly improved survival with medians of 46 d and 44 d, respectively. Intratumoral injection of Ad.RSV-G or a soluble RSV-F encoding adenovirus (Ad.RSV-F(sol)) had no significant anti-neoplastic effect. The median survival of these treatment groups and of Ad.Null-treated control animals was about 30 d.


CONCLUSIONS
Although in vitro transduction of colon cancer cell lines with Ad.RSV-F/G resulted in about 8-fold larger syncytia than with Ad.RSV-F, the in vivo outcome was not significantly different. Transduction of murine colon cancer cell lines with Ad.RSV-F or Ad.RSV-F/G caused apoptotic cell death, in contrast to transduction with Ad.RSV-G or Ad.RSV-F(sol), suggesting an importance of the mode of cell death. Overall, these findings provide insight into improved tumor vaccination strategies relying on the intratumoral expression of viral fusogenic membrane proteins.
Hoffmann
Dennis
D
Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Bldg. MA, Rm. 6/40, Bochum 44801, Germany.
Grunwald
Thomas
T
Bayer
Wibke
W
Wildner
Oliver
O
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D015726:Giant Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
D000970:Antineoplastic Agents; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins