An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma

Bo Xu, Rui Ma, Luke Russell, Ji Young Yoo, Jianfeng Han, Hanwei Cui, Ping Yi, Jianying Zhang, Hiroshi Nakashima, Hongsheng Dai, E. Antonio Chiocca, Balveen Kaur, Michael A. Caligiuri, Jianhua Yu

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin. Ectopically expressed E-cadherin enhanced the spread of OV-CDH1 by facilitating cell-to-cell infection and viral entry and reduced viral clearance by selectively protecting OV-CDH1-infected cells from KLRG1+ NK cell killing. In vivo, OV-CDH1 treatment substantially prolonged the survival in GBM-bearing mouse models, primarily because of improved viral spread rather than inhibition of NK cell activity. Thus, virus-induced overexpression of E-cadherin may be a generalizable strategy for improving cancer virotherapy.

Original languageEnglish (US)
Pages (from-to)45-62
Number of pages18
JournalNature Biotechnology
Issue number1
StatePublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


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