Gene therapy for
schwannomas was evaluated in two mouse models of
neurofibromatosis type 2 (NF2): (1) a transgenic model in which mice express a dominant mutant form of
merlin and spontaneously develop
schwannomas, and (2) a xenograft model in which human
schwannoma tissue is implanted subcutaneously into immune- compromised mice. In both models,
schwannoma volumes were monitored by magnetic resonance imaging (MRI) and showed strong
gadolinium enhancement typical of these
tumors in humans. Both types of
tumor were positive for the Schwann cell marker S100, and highly infectable with herpes simplex virus (HSV) vectors.
Schwannomas were injected with an oncolytic HSV-1 recombinant virus vector, G47Delta, which has deletions in genes for
ribonucleotide reductase (ICP6), gamma34.5, and ICP47. In the NF2 transgenic model,
schwannomas were reduced by more than half their original size by 10 days after
infection. In the case of subcutaneous
schwannoma xenografts, reduction in size after
infection occurred more slowly, with a mean reduction of onethird by 42 days
after treatment.
Schwannomas injected with control vehicles continued to grow slowly over time in both
schwannoma models. These studies demonstrate the ability of an oncolytic recombinant HSV vector to reduce the volume of
schwannoma tumors in NF2
tumor models in mice and extend the possible therapeutic applications of oncolytic vectors for benign
tumors to reduce mass while minimizing nerve damage.