Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion

Emmanouela Linardakis, Andrew Bateman, Vy Phan, Atique Ahmed, Michael Gough, Kenneth Olivier, Rick Kennedy, Fiona Errington, Kevin J. Harrington, Alan Melcher, Richard Vile

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78 Scopus citations

Abstract

We have investigated how to make K1735 cells, a poor allogeneic melanoma vaccine, more effective for protection against B16 in vivo. To promote antigen release in an immunologically effective manner, tumor cells were transfected with a viral fusogenic membrane glycoprotein (vesicular stomatitis virus G glycoprotein), which kills cells through the formation, and degeneration, of large multinucleated syncytia. Vaccines consisting of a 1:1 mix of fusing allogeneic and autologous cells led to dramatic increases in survival of mice in both prophylactic and therapy models, dependent upon T cells, the mechanism of tumor-tumor cell fusion, and the nature of the fusion partner. Syncytia activate macrophages and fusogenic membrane glycoprotein-mediated cell killing very efficiently promotes cross-priming of immature dendritic cells with a model tumor antigen. Our data suggest that the unique manner in which syncytia develop and die provides a highly effective pathway for tumor antigen release and presentation to the immune system and offers a novel mechanism by which cancer cell vaccines may be prepared for clinical use.

Original languageEnglish (US)
Pages (from-to)5495-5504
Number of pages10
JournalCancer research
Volume62
Issue number19
StatePublished - Oct 1 2002

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Linardakis, E., Bateman, A., Phan, V., Ahmed, A., Gough, M., Olivier, K., Kennedy, R., Errington, F., Harrington, K. J., Melcher, A., & Vile, R. (2002). Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion. Cancer research, 62(19), 5495-5504.