Authors
Yueh-Shan Weng, I-Tsang Chiang, Dai-Cheng Dong, Yu-Chang Liu, Keng-Li Lan, Chang-Liang Tsai, Fei-Ting Hsu
Published in
Cancer letters. Pages 218694. Jul 04, 2026. Epub Jul 04, 2026.
Abstract
Given the high heterogeneity and immunosuppressive nature of glioblastoma (GBM), standard monotherapies such as chemotherapy, radiotherapy, and immunotherapy show limited efficacy. Therefore, urgent combined treatment strategies-like immunostimulatory recombinant proteins-are needed. Compared to interleukin-2 (IL-2), IL-15 is a promising agent without the drawback of activation-induced cell death (AICD). We engineered a recombinant human IL-15 fused with an albumin-binding domain (hIL-15-ABD) to prolong IL-15's half-life and enhance blood-brain barrier penetration. We evaluated whether hIL-15-ABD could boost the efficacy of immune checkpoint inhibitors (ICIs) in a GBM model. Our findings indicate that hIL-15-ABD significantly improves the anti-GBM effects of anti-PD-L1 and anti-PD-1 therapies by increasing M1 macrophage populations, activating cytotoxic T cells, and promoting natural killer cell responses in an orthotopic GBM model. hIL-15-ABD enhanced the efficacy of both anti-PD-L1 (10F.9G2) in C57BL/6 mice and anti-PD-1 (nivolumab) in a GL261 model using humanized PD1+/+ mice. Notably, hIL-15-ABD not only boosts immunostimulation but also reduces the proportions of immunosuppressive cells, including regulatory T cells and MDSCs, in the tumor microenvironment. Additionally, hIL-15-ABD appears to target FGF-2 and its receptors, inactivating the FGF-2/FGFR1/2 pathways. In summary, hIL-15-ABD shows potential as an immunostimulatory agent for ICIs in GBM treatment.
PMID:
42401334
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.
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