PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance

Luke Russell, Jessica Swanner, Alena Cristina Jaime-Ramirez, Yufeng Wang, Alex Sprague, Yeshavanth Banasavadi-Siddegowda, Ji Young Yoo, Gina M. Sizemore, Raleigh Kladney, Jianying Zhang, Norman L. Lehman, Michael C. Ostrowski, Bangxing Hong, Michael Caligiuri, Jianhua Yu, Balveen Kaur

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Engineered oncolytic viruses are used clinically to destroy cancer cells and have the ability to boost anticancer immunity. Phosphatase and tensin homolog deleted on chromosome 10 loss is common across a broad range of malignancies, and is implicated in immune escape. The N-terminally extended isoform, phosphatase and tensin homolog deleted on chromosome 10 alpha (PTENα), regulates cellular functions including protein kinase B signaling and mitochondrial adenosine triphosphate production. Here we constructed HSV-P10, a replicating, PTENα expressing oncolytic herpesvirus, and demonstrate that it inhibits PI3K/AKT signaling, increases cellular adenosine triphosphate secretion, and reduces programmed death-ligand 1 expression in infected tumor cells, thus priming an adaptive immune response and overcoming tumor immune escape. A single dose of HSV-P10 resulted in long term survivors in mice bearing intracranial tumors, priming anticancer T-cell immunity leading to tumor rejection. This implicates HSV-P10 as an oncolytic and immune stimulating therapeutic for anticancer therapy.

Original languageEnglish (US)
Article number5006
JournalNature communications
Issue number1
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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