Multimodal glioma immunotherapy combining TLR9-targeted STAT3 antisense oligodeoxynucleotides with PD1 immune checkpoint blockade.

ABSTRACT:

Background

Therapeutic resistance in glioblastoma (GBM) is multifactorial and results from genetic heterogeneity, the immunoprivileged localization, and the potently tolerogenic microenvironment. Signal transducer and activator of transcription 3 (STAT3) plays a key role in both glioma cell survival and immune evasion, reinforcing GBM resistance.

Methods

Here, we describe a new cell-selective and double-stranded STAT3 antisense oligonucleotide (CpG-STAT3dsASO) for targeting human/mouse glioma cells and GAMs but not T cells. The oligonucleotide safety and efficacy against orthotopic GBM was assessed in immunocompetent or immunodeficient mice.

Results

CpG-STAT3dsASO injected intracranially/intratumorally was well-tolerated and reduced progression of human U251 GBM xenot

SUBMITTER: Hung CY 

PROVIDER: S-EPMC12526143 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature