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

Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion
Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion
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.
0008-5472
5495-5504
Linardakis, Emmanouela
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Bateman, Andrew
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Phan, Vy
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Ahmed, Atique
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Gough, Michael
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Olivier, Keneth
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Kennedy, Rick
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Errington, Fiona
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Harrington, Kevin J.
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Melcher, Alan
68cc1c3e-8ad3-4d82-b1fa-c2a46d05c7ba
Vile, Richard
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Linardakis, Emmanouela
a6f40ff3-4458-4f60-b474-58c82585db98
Bateman, Andrew
a851558d-8b9b-4020-b148-a239c2b26815
Phan, Vy
d0420994-e12f-4fad-a454-bee8d9bf9193
Ahmed, Atique
e60022bd-e2d5-42a3-bb22-8ba40e341407
Gough, Michael
690f0c98-228c-479d-9cec-3415a93467e7
Olivier, Keneth
6f07e879-3a51-4852-b72f-e62c30d8e12a
Kennedy, Rick
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Errington, Fiona
a73395e9-c5db-4352-9b74-603142bbedca
Harrington, Kevin J.
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Melcher, Alan
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Vile, Richard
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Linardakis, Emmanouela, Bateman, Andrew, Phan, Vy, Ahmed, Atique, Gough, Michael, Olivier, Keneth, Kennedy, Rick, Errington, Fiona, Harrington, Kevin J., Melcher, Alan and Vile, Richard (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.

Record type: Article

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.

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Published date: 1 October 2002

Identifiers

Local EPrints ID: 26439
URI: http://eprints.soton.ac.uk/id/eprint/26439
ISSN: 0008-5472
PURE UUID: 0efaf92a-6a21-40eb-af0c-e5395b2383f5

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Date deposited: 26 Apr 2006
Last modified: 15 Mar 2024 07:10

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Contributors

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

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