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Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice

Lien Van Hoecke (UGent) , Stephanie Riederer, Xavier Saelens (UGent) , Gerd Sutter and Juan Jose Rojas
(2020) ONCOIMMUNOLOGY. 9(1).
Author
Organization
Abstract
Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently reported that the intratumor expression of MLKL, a necroptosis inducing factor, generates a protective anti-tumor immunity. Here, we combined both approaches to test the use of VACV to deliver MLKL into the tumor. We generated VACV vectors expressing MLKL and evaluated the effects of MLKL on antitumor efficacy. In vitro infection of cancer cells with MLKL-expressing vectors led to cell death with necroptotic hallmarks. In syngeneic mouse tumor models, VACV expressing MLKL induced an outstanding antitumor activity, which was associated with a robust immunity directed against neo-epitopes. In conclusion, delivery of MLKL by VACV vectors boosts the intrinsic anti-tumor properties of these viral vectors by promoting in situ immunogenic cell death of infected cancer cells.
Keywords
IMMUNOGENIC CELL-DEATH, VACCINIA VIRUS, CHECKPOINT BLOCKADE, CANCER, VECTOR, Immunotherapy, necroptosis, MLKL, oncolytic virus, VACV

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MLA
Van Hoecke, Lien, et al. “Recombinant Viruses Delivering the Necroptosis Mediator MLKL Induce a Potent Antitumor Immunity in Mice.” ONCOIMMUNOLOGY, vol. 9, no. 1, Taylor & Francis Inc, 2020, doi:10.1080/2162402X.2020.1802968.
APA
Van Hoecke, L., Riederer, S., Saelens, X., Sutter, G., & Jose Rojas, J. (2020). Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice. ONCOIMMUNOLOGY, 9(1). https://doi.org/10.1080/2162402X.2020.1802968
Chicago author-date
Van Hoecke, Lien, Stephanie Riederer, Xavier Saelens, Gerd Sutter, and Juan Jose Rojas. 2020. “Recombinant Viruses Delivering the Necroptosis Mediator MLKL Induce a Potent Antitumor Immunity in Mice.” ONCOIMMUNOLOGY 9 (1). https://doi.org/10.1080/2162402X.2020.1802968.
Chicago author-date (all authors)
Van Hoecke, Lien, Stephanie Riederer, Xavier Saelens, Gerd Sutter, and Juan Jose Rojas. 2020. “Recombinant Viruses Delivering the Necroptosis Mediator MLKL Induce a Potent Antitumor Immunity in Mice.” ONCOIMMUNOLOGY 9 (1). doi:10.1080/2162402X.2020.1802968.
Vancouver
1.
Van Hoecke L, Riederer S, Saelens X, Sutter G, Jose Rojas J. Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice. ONCOIMMUNOLOGY. 2020;9(1).
IEEE
[1]
L. Van Hoecke, S. Riederer, X. Saelens, G. Sutter, and J. Jose Rojas, “Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice,” ONCOIMMUNOLOGY, vol. 9, no. 1, 2020.
@article{8683524,
  abstract     = {{Vaccinia viruses (VACV) are a novel class of immune-oncolytic therapeutics and their mechanism of action is based both on their capacity to replicate selectively in cancer cells and to elicit danger signals that can boost anti-tumor immunity. We recently reported that the intratumor expression of MLKL, a necroptosis inducing factor, generates a protective anti-tumor immunity. Here, we combined both approaches to test the use of VACV to deliver MLKL into the tumor. We generated VACV vectors expressing MLKL and evaluated the effects of MLKL on antitumor efficacy. In vitro infection of cancer cells with MLKL-expressing vectors led to cell death with necroptotic hallmarks. In syngeneic mouse tumor models, VACV expressing MLKL induced an outstanding antitumor activity, which was associated with a robust immunity directed against neo-epitopes. In conclusion, delivery of MLKL by VACV vectors boosts the intrinsic anti-tumor properties of these viral vectors by promoting in situ immunogenic cell death of infected cancer cells.}},
  articleno    = {{1802968}},
  author       = {{Van Hoecke, Lien and Riederer, Stephanie and Saelens, Xavier and Sutter, Gerd and Jose Rojas, Juan}},
  issn         = {{2162-402X}},
  journal      = {{ONCOIMMUNOLOGY}},
  keywords     = {{IMMUNOGENIC CELL-DEATH,VACCINIA VIRUS,CHECKPOINT BLOCKADE,CANCER,VECTOR,Immunotherapy,necroptosis,MLKL,oncolytic virus,VACV}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{5}},
  publisher    = {{Taylor & Francis Inc}},
  title        = {{Recombinant viruses delivering the necroptosis mediator MLKL induce a potent antitumor immunity in mice}},
  url          = {{http://doi.org/10.1080/2162402X.2020.1802968}},
  volume       = {{9}},
  year         = {{2020}},
}
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