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Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.

Publication ,  Journal Article
Holl, EK; Brown, MC; Boczkowski, D; McNamara, MA; George, DJ; Bigner, DD; Gromeier, M; Nair, SK
Published in: Oncotarget
November 29, 2016

Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, as clinically suitable 'oncolytic' viruses are severely attenuated and their spread and propagation are opposed by host immunity. Thus, a more propitious event in this context is the innate antiviral response to intratumoral virus administration, in particular for recruiting durable adaptive immune effector responses. It may represent a double-edged sword, as innate immune activation may eliminate infected tumor cells early, intercept viral spread and block any meaningful therapeutic response. The innate response to viral infection of tumors may be very different from that in non-malignant target tissues, owing to the unusual composition/tissue properties of tumor stroma. In this work, we report investigations of the innate immune response to the oncolytic poliovirus recombinant, PVSRIPO, in two mouse xenotransplantation models for breast and prostate cancer. Our observations indicate short-term virus persistence in infected tumors and virus recovery indicative of modest intratumoral propagation and persistence. Yet, a powerful innate inflammatory response coincided with chemokine induction and myeloid cell infiltration into tumors that was, interestingly, dominated by neutrophils. The combined effect of PVSRIPO tumor infection and the innate response it elicits was significant tumor regression in both models.

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 29, 2016

Volume

7

Issue

48

Start / End Page

79828 / 79841

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Transgenes
  • Prostatic Neoplasms
  • Poliovirus
  • Oncolytic Viruses
  • Oncolytic Virotherapy
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
 

Citation

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Holl, E. K., Brown, M. C., Boczkowski, D., McNamara, M. A., George, D. J., Bigner, D. D., … Nair, S. K. (2016). Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models. Oncotarget, 7(48), 79828–79841. https://doi.org/10.18632/oncotarget.12975
Holl, Eda K., Michael C. Brown, David Boczkowski, Megan A. McNamara, Daniel J. George, Darell D. Bigner, Matthias Gromeier, and Smita K. Nair. “Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.Oncotarget 7, no. 48 (November 29, 2016): 79828–41. https://doi.org/10.18632/oncotarget.12975.
Holl EK, Brown MC, Boczkowski D, McNamara MA, George DJ, Bigner DD, et al. Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models. Oncotarget. 2016 Nov 29;7(48):79828–41.
Holl, Eda K., et al. “Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.Oncotarget, vol. 7, no. 48, Nov. 2016, pp. 79828–41. Pubmed, doi:10.18632/oncotarget.12975.
Holl EK, Brown MC, Boczkowski D, McNamara MA, George DJ, Bigner DD, Gromeier M, Nair SK. Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models. Oncotarget. 2016 Nov 29;7(48):79828–79841.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

November 29, 2016

Volume

7

Issue

48

Start / End Page

79828 / 79841

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Transgenes
  • Prostatic Neoplasms
  • Poliovirus
  • Oncolytic Viruses
  • Oncolytic Virotherapy
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male