ArticleJHEP reports : innovation in hepatology2026
Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma.
Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Targeting the αvβ5 Integrin Modifies the TGFβ-Rich Tumor Microenvironment of Pancreatic Cancer.Cancer research · 2026Article
- Enhancing Immunotherapeutic Response in Colorectal Cancer with a Neuropilin 1-Targeting Tumor-Penetrating Peptide.Cancer research communications · 2026Article
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14 authors.
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Abstract
Background & Aims: Immune checkpoint inhibitor (ICI) therapy has significantly improved the treatment of solid tumors such as hepatocellular carcinoma (HCC); however, most patients fail to respond. Here, we examined whether co-administration of the tumor-penetrating internalizing (i)RGD peptide, which selectively increases tumor vascular permeability in a neuropilin-1-dependent manner, enhances intratumoral delivery and therapeutic efficacy of αPD-L1 in mouse models of HCC. Methods: αPD-L1, with or without iRGD, was administered intravenously to mice bearing endogenous HCCs (TGFα/c-myc and diethylnitrosamine [DEN]/carbon tetrachloride [CCl Results: While αPD-L1 monotherapy had minimal impact on tumor progression, combination treatment with iRGD significantly improved therapeutic efficacy, resulting in markedly reduced tumor growth (mean difference -198.2%, Conclusions: iRGD co-administration significantly improves the therapeutic efficacy of αPD-L1 in HCC mouse models by increasing intratumoral αPD-L1 delivery and more effectively alleviating the immunosuppressive tumor microenvironment. This non-conjugated, systemic approach holds strong translational potential to enhance ICI responses in patients with HCC. Impact and implications: Immune checkpoint inhibitors (ICIs) show limited efficacy in hepatocellular carcinoma (HCC), to which poor intratumoral drug delivery is likely to contribute. This study demonstrates that intravenous co-administration of the tumor-penetrating peptide iRGD with anti-PD-L1 significantly improves antibody distribution and therapeutic response without increasing toxicity in preclinical HCC models. These findings are highly relevant for clinicians and researchers aiming to enhance ICI effectiveness in solid tumors. Given the ongoing clinical evaluation of iRGD, this simple, non-conjugated strategy offers a feasible and rapidly translatable approach to overcome a key limitation of current ICI therapy and improve outcomes for patients with HCC.
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