Shifting Immune Balance to Extend Oncolytic Virus Response in Malignant Peripheral Nerve Sheath Tumors
Abstract
The most common cause of death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). Unfortunately, other than surgery, our currently available cancer treatments are not effective for MPNSTs. Often the tumors are too large and have already spread by the time they are discovered, making surgery ineffective. We need new and more effective therapies. Viruses such as the recently Food and Drug Administration (FDA)-approved T-VEC, created from the cold sore virus, can infect and kill tumor cells, making virus therapy (or “virotherapy”) a potential treatment. Our earlier work showed that, while many MPNSTs are treatable with virotherapy, almost half of the tested tumor cell samples resisted infection. We have now identified a way to treat these more resistant MPNSTs by using a commercially available medication and then treating with a next-generation virus that I developed. We now have proof that this approach works in animals and we can treat the most virus-resistant tumor. Our results show that making the virus replicate well so that it can stimulate the immune response against cancer cells is critical for this therapy. In this proposal, we examine how to further improve this therapy by enhancing the immune response against the tumor. While all of the studies in this proposal are in mouse models, our approach can be rapidly translated to patients, and these studies will help us design more effective clinical trials for patients. Furthermore, the data we generate from these animal models are essential for when we contact the FDA and request combining our virus with these medications in future clinical trials. Our findings could result in a new clinical trial right away, as most of the drugs and even the viruses we are testing in this proposal are approved for clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010340
Entities
People
- Kevin Cassady
Organizations
- United States Army