Oncolytic herpes simplex virus immunovirotherapy in combination with immune checkpoint blockade to treat glioblastoma

Immunotherapy
Dipongkor SahaSamuel D Rabkin

Abstract

Oncolytic viruses, such as oncolytic herpes simplex virus (oHSV), are a new class of cancer therapeutic, which selectively replicate and kill cancer cells, while inducing an inflammatory microenvironment, immunovirotherapy. Recently, an oHSV (talimogene laherparepvec) has been approved for the treatment of advanced melanoma. Glioblastoma (GBM) is an almost always lethal primary tumor in the brain that is highly immunosuppressive, and posited to contain GBM stem-like cells (GSCs). Immune checkpoint blockade has revolutionized therapy for some cancers, but not GBM. We have used a syngeneic GSC-derived orthotopic GBM model (005) to develop immunotherapeutic strategies. Curative therapy required oHSV expressing IL-12 in combination with two checkpoint inhibitors, anti-PD-1 and anti-CTLA-4. This response required CD4+ and CD8+ T cells, and macrophages in a complex interplay.

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Citations

May 28, 2020·Journal for Immunotherapy of Cancer·Dipongkor SahaRobert L Martuza
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Methods Mentioned

BETA
transgenic

Clinical Trials Mentioned

NCT03152318

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