Nature Communications | ( 2026) 17:2893
Abstract:
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.
Full Article: https://www.klebergfoundation.org/wp-content/uploads/2026/04/Chheda_Nature-Communications.pdf
