Developing New Therapeutic Strategies for Malignant Peripheral Nerve Sheath Tumor By Interrupting Immunologic Tolerance

ABSTRACT

Despite some interruptions in workflow and data acquisition due to the COVID pandemic, we made substantial progress this past year towards our aims. We completed most of the studies in aims 1 and 2 to compare our panel of viruses in one (#5NPCIS) of the two tumor models. We found that TVEC had the most ability to replicate in cell lines, but by other parameters the three viruses functioned similarly in their relative lack of therapeutic efficacy as a single agent despite induction of immune cell chemoattractant chemokines and immune cell infiltration. We encountered unforeseen challenges in growing the second model (67C-4), but those have largely been solved and we are now poised to complete aims 1 and 2 using that model in the final year of the project. We also conducted studies in the first model of combinationtherapy as planned in aim 2, but also found no combination efficacy. These results were surprising to us, as the combination has shown activity in other tumors types, including a model of rhabdomyosarcoma which is also an NF-1 related tumor. Again, we will test combination therapy as described in aim 2 in the second model in the coming year of the grant. Finally, we also made progress on aim 3 using virus plus ruxolitinib, and plan to complete those studies in the next reporting period.