Cargando…

Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms

Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting an...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Dae-Sun, Dastidar, Himika, Zhang, Chunfen, Zemp, Franz J., Lau, Keith, Ernst, Matthias, Rakic, Andrea, Sikdar, Saif, Rajwani, Jahanara, Naumenko, Victor, Balce, Dale R., Ewanchuk, Ben W., Tailor, Pankaj, Yates, Robin M., Jenne, Craig, Gafuik, Chris, Mahoney, Douglas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570934/
https://www.ncbi.nlm.nih.gov/pubmed/28839138
http://dx.doi.org/10.1038/s41467-017-00324-x
_version_ 1783259251030884352
author Kim, Dae-Sun
Dastidar, Himika
Zhang, Chunfen
Zemp, Franz J.
Lau, Keith
Ernst, Matthias
Rakic, Andrea
Sikdar, Saif
Rajwani, Jahanara
Naumenko, Victor
Balce, Dale R.
Ewanchuk, Ben W.
Tailor, Pankaj
Yates, Robin M.
Jenne, Craig
Gafuik, Chris
Mahoney, Douglas J.
author_facet Kim, Dae-Sun
Dastidar, Himika
Zhang, Chunfen
Zemp, Franz J.
Lau, Keith
Ernst, Matthias
Rakic, Andrea
Sikdar, Saif
Rajwani, Jahanara
Naumenko, Victor
Balce, Dale R.
Ewanchuk, Ben W.
Tailor, Pankaj
Yates, Robin M.
Jenne, Craig
Gafuik, Chris
Mahoney, Douglas J.
author_sort Kim, Dae-Sun
collection PubMed
description Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8(+) T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8(+) T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSV(ΔM51)) promotes CD8(+) T-cell accumulation within tumors and CD8(+) T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSV(ΔM51) therapy engenders CD8(+) T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity.
format Online
Article
Text
id pubmed-5570934
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-55709342017-08-30 Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms Kim, Dae-Sun Dastidar, Himika Zhang, Chunfen Zemp, Franz J. Lau, Keith Ernst, Matthias Rakic, Andrea Sikdar, Saif Rajwani, Jahanara Naumenko, Victor Balce, Dale R. Ewanchuk, Ben W. Tailor, Pankaj Yates, Robin M. Jenne, Craig Gafuik, Chris Mahoney, Douglas J. Nat Commun Article Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8(+) T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8(+) T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSV(ΔM51)) promotes CD8(+) T-cell accumulation within tumors and CD8(+) T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSV(ΔM51) therapy engenders CD8(+) T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity. Nature Publishing Group UK 2017-08-24 /pmc/articles/PMC5570934/ /pubmed/28839138 http://dx.doi.org/10.1038/s41467-017-00324-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Dae-Sun
Dastidar, Himika
Zhang, Chunfen
Zemp, Franz J.
Lau, Keith
Ernst, Matthias
Rakic, Andrea
Sikdar, Saif
Rajwani, Jahanara
Naumenko, Victor
Balce, Dale R.
Ewanchuk, Ben W.
Tailor, Pankaj
Yates, Robin M.
Jenne, Craig
Gafuik, Chris
Mahoney, Douglas J.
Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title_full Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title_fullStr Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title_full_unstemmed Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title_short Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
title_sort smac mimetics and oncolytic viruses synergize in driving anticancer t-cell responses through complementary mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570934/
https://www.ncbi.nlm.nih.gov/pubmed/28839138
http://dx.doi.org/10.1038/s41467-017-00324-x
work_keys_str_mv AT kimdaesun smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT dastidarhimika smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT zhangchunfen smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT zempfranzj smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT laukeith smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT ernstmatthias smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT rakicandrea smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT sikdarsaif smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT rajwanijahanara smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT naumenkovictor smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT balcedaler smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT ewanchukbenw smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT tailorpankaj smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT yatesrobinm smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT jennecraig smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT gafuikchris smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms
AT mahoneydouglasj smacmimeticsandoncolyticvirusessynergizeindrivinganticancertcellresponsesthroughcomplementarymechanisms