ArticleJournal for immunotherapy of cancer2021
Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Immunotherapy for Leiomyosarcoma: Current Status and Perspectives.Journal of immunology research · 2026Review
- Targeted 2-Deoxy-D-Ribose Delivery by Biomimetic Nanoplatform Activates EGFR for Accelerated Heart Valve Endothelialization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Intravenous iRGD-Guided, RBC-Membrane Camouflaged Lactococcus Lactis Remodels Cold NSCLC and Enhances PD-1 Blockade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Novel molecular mechanisms of immune evasion in hepatocellular carcinoma: NSUN2-mediated increase of SOAT2 RNA methylation.Cancer communications (London, England) · 2025Article
- The MYC/TXNIP axis mediates NCL-Suppressed CD8Molecular medicine (Cambridge, Mass.) · 2025Article
- Targeted editing of CCL5 with CRISPR-Cas9 nanoparticles enhances breast cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2025Article
- Unveiling the key mechanisms of FOLR2+ macrophage-mediated antitumor immunity in breast cancer using integrated single-cell RNA sequencing and bulk RNA sequencing.Breast cancer research : BCR · 2025Article
- Advances and prospects of cell-penetrating peptides in tumor immunotherapy.Scientific reports · 2025Review
- TCR-T cell therapy for solid tumors: challenges and emerging solutions.Frontiers in pharmacology · 2025Review
- 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
- PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8Apoptosis : an international journal on programmed cell death · 2024Article
- Engineered Cancer Nanovaccines: A New Frontier in Cancer Therapy.Nano-micro letters · 2024Review
- Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.Biomolecules & biomedicine · 2024Article
- CD3-engaging bispecific antibodies trigger a paracrine regulated wave of T-cell recruitment for effective tumor killing.Communications biology · 2024Article
- Single-cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism-related mechanisms.Clinical and translational medicine · 2024Article
- Tumour-specific activation of a tumour-blood transport improves the diagnostic accuracy of blood tumour markers in mice.EBioMedicine · 2024Article
- Glycoengineering-based anti-PD-1-iRGD peptide conjugate boosts antitumor efficacy through T cell engagement.Cell reports. Medicine · 2024Article
- Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer.EMBO molecular medicine · 2024Article
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPoor infiltration and limited activation of transferred T cells are fundamental factors impeding the development of adoptive cell immunotherapy in solid tumors. A tumor-penetrating peptide iRGD has been widely used to deliver drugs deep into tumor tissues. CD3-targeting bispecific antibodies represent a promising immunotherapy which recruits and activates T cells.
methodsT-cell penetration was demonstrated in tumor spheroids using confocal microscope, and in xenografted tumors by histology and in vivo real-time fluorescence imaging. Activation and cytotoxicity of T cells were assessed by flow cytometry and confocal microscope. Bioluminescence imaging was used to evaluate in vivo antitumor effects, and transmission electron microscopy was used for mechanistic studies.
resultsWe generated a novel bifunctional agent iRGD-anti-CD3 which could immobilize iRGD on the surface of T cells through CD3 engaging. We found that iRGD-anti-CD3 modification not only facilitated T-cell infiltration in 3D tumor spheroids and xenografted tumor nodules but also induced T-cell activation and cytotoxicity against target cancer cells. T cells modified with iRGD-anti-CD3 significantly inhibited tumor growth and prolonged survival in several xenograft mouse models, which was further enhanced by the combination of programmed cell death protein 1 (PD-1) blockade. Mechanistic studies revealed that iRGD-anti-CD3 initiated a transport pathway called vesiculovacuolar organelles in the endothelial cytoplasm to promote T-cell extravasation.
conclusionAltogether, we show that iRGD-anti-CD3 modification is an innovative and bifunctional strategy to overcome major bottlenecks in adoptive cell therapy. Moreover, we demonstrate that combination with PD-1 blockade can further improve antitumor efficacy of iRGD-anti-CD3-modified T cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.