ArticleJournal of translational medicine2023
iRGD-modified memory-like NK cells exhibit potent responses to hepatocellular carcinoma.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- Current development and challenges of NK cell-based immunotherapy for gastrointestinal cancers.International journal of clinical oncology · 2026Review
- Immunotherapy for Leiomyosarcoma: Current Status and Perspectives.Journal of immunology research · 2026Review
- Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.Cancer communications (London, England) · 2026Review
- Cytokine preactivation and ADCC: a potent strategy for enhancing human NK cell effector functions against 3D tumor models.Frontiers in immunology · 2026Article
- Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors.Signal transduction and targeted therapy · 2025Article
- Ultrasoft hydrogel immune millirobot with multimodal locomotion.Science advances · 2025Article
- Intravenous iRGD-Guided, RBC-Membrane Camouflaged Lactococcus Lactis Remodels Cold NSCLC and Enhances PD-1 Blockade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.Clinical pharmacology in drug development · 2025Article
- Advances and prospects of cell-penetrating peptides in tumor immunotherapy.Scientific reports · 2025Review
- iRGD Tumor Penetrating Peptide-Modified NK Cells Exhibit Enhanced Tumor Immune Infiltration Ability and Anti-Tumor Efficacy.Protein and peptide letters · 2025Article
- Tumor-penetrating peptide boosts bispecific T-cell engager antitumor efficacy for the pancreatic cancer.Frontiers in immunology · 2025Article
- Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation.Human vaccines & immunotherapeutics · 2024Article
- DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy.Molecular biology reports · 2024Article
- Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems.Cancers · 2024Review
- Correction: iRGD-modified memory-like NK cells exhibit potent responses to hepatocellular carcinoma.Journal of translational medicine · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCytokine-induced memory-like natural killer (CIML NK) cells have been found to possess potent antitumor responses and induce complete remissions in patients with leukemia. However, the poor infiltration of transferred NK cells is a major obstacle in developing adoptive cell immunotherapy for solid tumors. In our study, we explored the potential of using the tumor-penetrating peptide iRGD to deliver activated CIML NK cells deep into tumor tissues.
methodsAfter being briefly stimulated with interleukin-12 (IL-12), IL-15, and IL-18, CIML NK cells were assessed for their phenotype and function with flow cytometry. The penetrating and killing capability of iRGD-modified CIML NK cells in tumor spheroids was revealed by confocal microscopy. The anti-tumor efficacy of these modified CIML NK cells was tested in hepatocellular carcinoma (HCC) xenograft mouse models.
resultsTreating NK cells with cytokines led to a substantial activation, which was evidenced by the upregulation of CD25 and CD137. After a resting period of six days, CIML NK cells were still able to display strong activation when targeting HepG2 and SK-Hep-1 HCC cell lines. Additionally, CIML NK cells produced increased amounts of cytokines (interferon-gamma and tumor necrosis factor alpha) and exhibited heightened cytotoxicity towards HCC cell lines. The iRGD modification enabled CIML NK cells to infiltrate multicellular spheroids (MCSs) and, consequently, to induce cytotoxicity against the target cancer cells. Moreover, the CIML NK cells modified with iRGD significantly decreased tumor growth in a HCC xenograft mouse model.
conclusionOur findings demonstrate that CIML NK cells possess augmented potency and durability against HCC cell lines in vitro. Additionally, we have seen that the incorporation of iRGD to CIML NK cells facilitates enhanced infiltration and targeted destruction of MCSs. Moreover, the application of iRGD-modified CIML NK cells reveal remarkable anti-tumor efficacy against HCC in vivo.
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