Long-acting interleukin-7 improves the efficacy of oncolytic viral therapy in glioblastoma

作者：Yuping Derek Li, David A. Giles, Yi Huang, Ashwani Kesarwani, Tong Hu, Loǵan Waller Paǵe, Amanda De Andrade Costa, Jingqin Luo, Alexandra A. Wolfarth, Donghoon Choi, Tu Dang, Albert H. Kim, John F. DiPersio, David T. Curiel, Michael S. Diamond, Milan Chheda · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-69606-7 · 被引用次数：1 · 研究领域：Virus-based gene therapy research、CAR-T cell therapy research、interferon and immune responses

Despite advances in immunotherapy, the prognosis for patients with glioblastoma (GBM) remains poor. The efficacy of GBM-targeted immunotherapies is limited by the paucity of functional T cells in the tumor microenvironment, a consequence of the local and systemic immunosuppression prevalent in patients with GBM. To overcome these challenges, here we develop a treatment strategy we term “expand and pull,” which uses systemic administration of rhIL-7-hyFc, a long-acting recombinant human interleukin-7, to increase peripheral T cell abundance (“expand”), followed by intratumoral oncolytic virus treatment to recruit these cells to the tumor microenvironment (“pull”). We show that rhIL-7-hyFc improves the efficacy of multiple oncolytic viral therapies in syngeneic immuno-resistant mouse models of glioma. Combining rhIL-7-hyFc and Zika virus (ZIKV) increases systemic and intratumoral T cell abundance, improves cytotoxic T cell function, and delays expression of inhibitory checkpoint receptors, resulting in long-term tumor-free survival. We observe similar survival efficacy in experiments using a safer, genetically modified Δ10 3′-UTR ZIKV, as well as the clinically tested oncolytic adenovirus, Delta24-RGD. Collectively, our findings demonstrate that augmentation of both the systemic and local immune responses improves the utility of GBM-targeted immunotherapies. Oncolytic viruses, including Zika virus, have been proposed as therapeutic option for glioblastoma (GBM) treatment, howev...