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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月17日

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  • Yuping Derek Li,
  • David A. Giles,
  • Yi Huang,
  • Ashwani Kesarwani,
  • Tong Hu,
  • Logan Page,
  • Amanda de Andrade Costa,
  • Jingqin Luo,
  • Alexandra Wolfarth,
  • Donghoon Choi,
  • Mai T. Dang,
  • Albert H. Kim,
  • John F. DiPersio,
  • David T. Curiel,
  • Michael S. Diamond,
  • Milan G. Chheda

摘要

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.