DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Immunotherapy for NF2 Vestibular Schwannomas

Principal Investigator: XU, LEI
Institution Receiving Award: MASSACHUSETTS GENERAL HOSPITAL
Program: NFRP
Proposal Number: NF150030
Award Number: W81XWH-16-1-0219
Funding Mechanism: New Investigator Award
Partnering Awards:
Award Amount: $722,625.00


PUBLIC ABSTRACT

Neurofibromatosis type II (NF2) is a disease that needs new solutions. Radiation therapy (RT) is one of the main standard treatments of growing vestibular schwannoma (VS). However, radiation toxicity can lead to debilitating hearing loss, which translates to social impairment and increased depression. The ability of bevacizumab to improve hearing in patients with progressive VS has stimulated interest in anti-angiogenic therapy for schwannomas. However, its effect on hearing is not durable, and some patients are unable to tolerate long-term treatment due to toxic side effects. Therefore, the development of a novel therapy with enhanced efficacy and minimized toxicity-related hearing loss in VS is urgently needed.

Immunotherapy is designed to enhance the specific, potent, and durable anti-tumor responses imparted by the host immune system. Immunotherapy has achieved noteworthy benefit for patients with challenging malignant cancers and lymphoid malignancies. However, as a benign tumor, little is known whether NF2 patients are immune suppressed or whether immunotherapy is effective in combating the benign VS. Thus, we propose to study, in mouse models, the potential of immunotherapy to control tumor progression and enhance survival. We will further determine whether combining immunotherapy with anti-VEGF treatment will achieve enhanced efficacy, and how to best combine the two treatment modalities. Our data will directly inform the design of future clinical trials of immunotherapy in NF2 VS patients. As the antibodies for immunotherapy are currently being tested in clinical trials, our findings have the potential for rapid translation to the clinic to improve treatment of NF2 VS.