IMMU-39. NANOPARTICLE TREATMENT REBALANCES IMMUNODOMINANCE OF ANTI-VIRUS IMMUNITY TO ENHANCE ANTI-TUMOR IMMUNITY DURING ONCOLYTIC ADENOVIRUS THERAPY IN SOLID TUMORS

Abstract Oncolytic virotherapy shows great potential for treating brain tumors and other solid that metastasize to the brain. A phase I clinical trial testing oncolytic adenovirus Delta-24-RGD (DNX-2401) in patients with recurrent malignant gliomas demonstrated significant benefits a subset of patients, another pediatric also indicated similar benefits. However, virus injection initiates both anti-virus anti-tumor immune responses by activating respective clones CD8+ T-cells, which compete limited resources clonal expansion. Expansion T-cells against highly immunogenic viral antigens might limit expansion subdominant tumor antigens. We hypothesized inducing tolerance dominant will allow previously tumor-specific T-cells. In this work, we observed nanoparticles encapsulating adenoviral successfully induced These were taken up liver resident macrophages, are involved maintaining peripheral tolerance. RNA-sequencing revealed recognizing encapsulated had unique transcriptome signatures upregulation genes specifically tolerance, including coinhibitory molecules. Virus-specific using redirected focus response towards melanoma as measured interferon-gamma secretion (P < 0.0001). Reduction virus-specific simultaneous T-cell confirmed tetramer staining 0.05). Importantly, combination nanoparticle-induced increased percentage long-term survivors compared treatment alone (100% versus 50%). Our data provide basis develop future trials aim maximize cancer tumors.