| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
Molecular Medicine Program [A. R. B., K. J. H., T. K., A. A., A. A. M., M. J. G., E. L., D. R., T. P., R. S., R. G. V.], Department of Oncology Research [A. D.], Section of Biostatistics [C. M. L.], Department of Otorhinolaryngology [S. S.], Mayo Clinic, Rochester, Minnesota 55905
Expression of viral fusogenic membrane glycoproteins (FMGs) is a potent strategy for antitumor cytotoxic gene therapy in which tumor cells are fused into large multinucleated syncytia. To understand how local cell killing can potentiate activation of antitumor immune responses, we characterized the mechanism of FMG-mediated cell killing. Here, we show that syncytia are highly ordered structures over 24–48 h but then die through processes that, by multiple morphological and biochemical criteria, bear very little resemblance to classical apoptosis. Death of syncytia is associated with nuclear fusion and premature chromosome condensation as well as severe ATP depletion and autophagic degeneration, accompanied by release of vesicles reminiscent of exosomes (syncytiosomes). Dying syncytia produce significantly more syncytiosomes than normal cells or cells killed by irradiation, freeze thaw, or osmotic shock. These syncytiosomes also load dendritic cells (DCs) more effectively than exosomes from cells dying by other mechanisms. Finally, we demonstrate that syncytiosomes from either autologous or allogeneic fusing melanoma cells lead to cross-presentation of a defined tumor antigen, gp100, by DCs to a gp100-specific CTL clone. Cross-presentation was significantly more efficient than that with exosomes from normal, irradiated, or herpes simplex virus thymidine kinase/ganciclovir-killed tumor cells. Therefore, FMG-mediated cell killing combines very effective local tumor cell killing with the potential to be a highly immunogenic method of cytotoxic gene therapy. In addition, these data open the way for novel methods of loading DCs with relevant tumor-associated antigens for vaccine development.
This article has been cited by other articles:
|
|
 |
|
  C.-P. Mao, C.-F. Hung, T. H. Kang, L. He, Y.-C. Tsai, C.-Y. Wu, and T.-C. Wu Combined Administration with DNA Encoding Vesicular Stomatitis Virus G Protein Enhances DNA Vaccine Potency J. Virol., March 1, 2010; 84(5): 2331 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Prestwich, F. Errington, E. J. Ilett, R. S.M. Morgan, K. J. Scott, T. Kottke, J. Thompson, E. E. Morrison, K. J. Harrington, H. S. Pandha, et al. Tumor Infection by Oncolytic Reovirus Primes Adaptive Antitumor Immunity Clin. Cancer Res., November 15, 2008; 14(22): 7358 - 7366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Gainey, M. J. Manuse, and G. D. Parks A Hyperfusogenic F Protein Enhances the Oncolytic Potency of a Paramyxovirus Simian Virus 5 P/V Mutant without Compromising Sensitivity to Type I Interferon J. Virol., October 1, 2008; 82(19): 9369 - 9380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vigil, M.-S. Park, O. Martinez, M. A. Chua, S. Xiao, J. F. Cros, L. Martinez-Sobrido, S. L.C. Woo, and A. Garcia-Sastre Use of Reverse Genetics to Enhance the Oncolytic Properties of Newcastle Disease Virus Cancer Res., September 1, 2007; 67(17): 8285 - 8292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hoffmann, W. Bayer, T. Grunwald, and O. Wildner Intratumoral expression of respiratory syncytial virus fusion protein in combination with cytokines encoded by adenoviral vectors as in situ tumor vaccine for colorectal cancer Mol. Cancer Ther., July 1, 2007; 6(7): 1942 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, A. Dutuor, L. Tao, X. Fu, and X. Zhang Virotherapy with a Type 2 Herpes Simplex Virus-Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma Clin. Cancer Res., January 1, 2007; 13(1): 316 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Fu, L. Tao, M. Li, W. E. Fisher, and X. Zhang Effective treatment of pancreatic cancer xenografts with a conditionally replicating virus derived from type 2 herpes simplex virus. Clin. Cancer Res., May 15, 2006; 12(10): 3152 - 3157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Errington, A. Bateman, T. Kottke, J. Thompson, K. Harrington, A. Merrick, P. Hatfield, P. Selby, R. Vile, and A. Melcher Allogeneic Tumor Cells Expressing Fusogenic Membrane Glycoproteins as a Platform for Clinical Cancer Immunotherapy Clin. Cancer Res., February 15, 2006; 12(4): 1333 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Efferson, N. Tsuda, K. Kawano, E. Nistal-Villan, S. Sellappan, D. Yu, J. L. Murray, A. Garcia-Sastre, and C. G. Ioannides Prostate Tumor Cells Infected with a Recombinant Influenza Virus Expressing a Truncated NS1 Protein Activate Cytolytic CD8+ Cells To Recognize Noninfected Tumor Cells J. Virol., January 1, 2006; 80(1): 383 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Salsman, D. Top, J. Boutilier, and R. Duncan Extensive Syncytium Formation Mediated by the Reovirus FAST Proteins Triggers Apoptosis-Induced Membrane Instability J. Virol., July 1, 2005; 79(13): 8090 - 8100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chang, P.-T. Chen, G.-D. Chang, C.-J. Huang, and H. Chen Functional Characterization of the Placental Fusogenic Membrane Protein Syncytin Biol Reprod, December 1, 2004; 71(6): 1956 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ebert, K. Shinozaki, C. Kournioti, M.-S. Park, A. Garcia-Sastre, and S. L. C. Woo Syncytia Induction Enhances the Oncolytic Potential of Vesicular Stomatitis Virus in Virotherapy for Cancer Cancer Res., May 1, 2004; 64(9): 3265 - 3270. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
