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Updated: Feb 17, 2026
Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Treatment of orthotopic malignant peripheral nerve sheath tumors with oncolytic herpes simplex virus
Slawomir Antoszczyk1, Melanie Spyra1, Victor Felix Mautner1
1Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.A., R.L.M., S.D.R.); Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (A.O.S.R.); Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., V.F.M.); Berlin-Brandenburg Center for Regenerative Therapies, Charité Medical University, Berlin, Germany (A.K.); College of Veterinary Medicine, Seoul National University, Seoul, Korea (A.K.).
Backgrounds:
Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive and often lethal sarcoma that frequently develops in patients with neurofibromatosis type 1 (NF1). We developed new preclinical MPNST models and tested the efficacy of oncolytic herpes simplex viruses (oHSVs), a promising cancer therapeutic that selectively replicates in and kills cancer cells.
Methods:
Mouse NF1(-) MPNST cell lines and human NF1(-) MPNST stemlike cells (MSLCs) were implanted into the sciatic nerves of immunocompetent and athymic mice, respectively. Tumor growth was followed by external measurement and sciatic nerve deficit using a hind-limb scoring system. Oncolytic HSV G47Δ as well as "armed" G47Δ expressing platelet factor 4 (PF4) or interleukin (IL)-12 were injected intratumorally into established sciatic nerve tumors.
Results:
Mouse MPNST cell lines formed tumors with varying growth kinetics. A single intratumoral injection of G47Δ in sciatic nerve tumors derived from human S462 MSLCs in athymic mice or mouse M2 (37-3-18-4) cells in immunocompetent mice significantly inhibited tumor growth and prolonged survival. Local IL-12 expression significantly improved the efficacy of G47Δ in syngeneic mice, while PF4 expression prolonged survival. Injection of G47Δ directly into the sciatic nerve of athymic mice resulted in only mild symptoms that did not differ from phosphate buffered saline control.
Conclusions:
Two new orthotopic MPNST models are described, including in syngeneic mice, expanding the options for preclinical testing. Oncolytic HSV G47Δ exhibited robust efficacy in both immunodeficient and immunocompetent MPNST models while maintaining safety. Interleukin-12 expression improved efficacy. These studies support the clinical translation of G47Δ for patients with MPNST.
Insights
Oncolytic herpes simplex virus (oHSV) G47Δ effectively reduced malignant peripheral nerve sheath tumor (MPNST) growth in new preclinical models. Interleukin-12 enhanced oHSV efficacy, supporting clinical translation for MPNST patients.
Area of Science:
- Oncology
- Virology
- Preclinical Cancer Models
Background:
- Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas often linked to neurofibromatosis type 1 (NF1).
- Oncolytic herpes simplex viruses (oHSVs) show promise for cancer therapy by selectively targeting and destroying cancer cells.
Purpose of the Study:
- To develop and characterize novel preclinical models for MPNSTs.
- To evaluate the therapeutic efficacy and safety of the oncolytic HSV G47Δ, including armed variants, in these new MPNST models.
Main Methods:
- Established orthotopic MPNST models using mouse NF1(-) cell lines and human MPNST stem-like cells (MSLCs) in immunocompetent and athymic mice.
- Administered intratumoral injections of oHSV G47Δ, or G47Δ armed with platelet factor 4 (PF4) or interleukin (IL)-12, into established sciatic nerve tumors.
- Monitored tumor growth and neurological deficits.
Main Results:
- oHSV G47Δ significantly inhibited tumor growth and prolonged survival in both mouse and human-derived MPNST models.
- IL-12 armed G47Δ demonstrated enhanced therapeutic efficacy in syngeneic mouse models, while PF4 armed G47Δ prolonged survival.
- Intratumoral G47Δ injection showed a favorable safety profile with only mild, transient symptoms.
Conclusions:
- Two new orthotopic MPNST models, including a syngeneic model, were established for advanced preclinical testing.
- Oncolytic HSV G47Δ demonstrated significant efficacy and safety in diverse MPNST models.
- The findings support the clinical development of G47Δ for treating MPNST, particularly with IL-12 augmentation.
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