Replication-competent herpes simplex virus retargeted to HER2 as therapy for high-grade glioma.

Molecular Therapy : the Journal of the American Society of Gene Therapy
E GambiniP Malatesta

Abstract

Oncolytic herpes simplex viruses (HSVs) represent a novel frontier against tumors resistant to standard therapies, like glioblastoma (GBM). The oncolytic HSVs that entered clinical trials so far showed encouraging results; however, they are marred by the fact that they are highly attenuated. We engineered HSVs that maintain unimpaired lytic efficacy and specifically target cells that express tumor-specific receptors, thus limiting the cytotoxicity only to cancer cells, and leaving unharmed the neighboring tissues. We report on the safety and efficacy in a high-grade glioma (HGG) model of R-LM113, an HSV recombinant retargeted to human epidermal growth factor receptor 2 (HER2), frequently expressed in GBMs. We demonstrated that R-LM113 is safe in vivo as it does not cause encephalitis when intracranially injected in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, extremely sensitive to wild-type HSV. The efficacy of R-LM113 was assessed in a platelet-derived growth factor (PDGF)-induced infiltrative glioma model engineered to express HER2 and transplanted intracranially in adult NOD/SCID mice. Mice injected with HER2-engineered glioma cells infected with R-LM113 showed a doubled survival time compared with mic...Continue Reading

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Citations

Oct 17, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hiroaki UchidaJoseph C Glorioso
Sep 21, 2012·Journal of Neurology, Neurosurgery, and Psychiatry·Alex TobiasMaciej S Lesniak
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Nov 11, 2020·International Journal of Molecular Sciences·Laura Menotti, Elisa Avitabile
Mar 5, 2021·Oncolytic Virotherapy·Hong-My Nguyen, Dipongkor Saha

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