ArticleAdvanced materials (Deerfield Beach, Fla.)2021
mRNA Delivery of a Bispecific Single-Domain Antibody to Polarize Tumor-Associated Macrophages and Synergize Immunotherapy against Liver Malignancies.
Article in Advanced materials (Deerfield Beach, Fla.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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The trial behind it
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Who cites it
98 citing papers in PubMed, 131 citations in OpenAlex.
- [Novel therapeutic strategies for liver metastases driven by the common microenvironment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Systemically delivered mRNA-LNPs transfect primary and secondary liver tumors.Molecular therapy. Nucleic acids · 2026Article
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 2026Review
- Personalized cancer vaccines: bridging immune-oncology and precision medicine for advanced therapeutics.Signal transduction and targeted therapy · 2026Review
- Upregulation of macrophage UPP1 promotes lung adenocarcinoma metastasis through an mtROS-cGAS-NLRP3 inflammasome axis.Cell death discovery · 2026Article
- mRNA vaccines for hepatocellular carcinoma: mechanisms, therapeutic strategies, and clinical perspectives.Hepatology international · 2026Review
- Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity.Cancer cell · 2026Article
- Personalized immunotherapy in HCC: synthesis, delivery, and clinical progress of mRNA-based vaccines.Cancer cell international · 2026Review
- Dual-targeted lipid nanoparticles for TET3 siRNA delivery: nanobiotechnology strategy to remodel tumor immune microenvironment in hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
- Shooting two hawks with one arrow: manganese-doped mesoporous carriers coordinate STING activation and enhanced mRNA translation forMaterials today. Bio · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Nanomaterial-Enabled Modulation of Tumor-Associated Macrophages and Dendritic Cells to Enhance Cancer Immunotherapy.Nanomaterials (Basel, Switzerland) · 2026Review
- Lipid nanoparticles and extracellular vesicles: emerging cell free therapeutic platforms for hepatobiliary cancers.Frontiers in cell and developmental biology · 2026Review
- TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives.Theranostics · 2026Review
- Nanoparticles that modulate immune cells - an important strategy for the future treatment of tumors.Frontiers in immunology · 2026Review
- Intraperitoneal Co-Delivery of Claudin18.2×41BB and EpCAM×CD3 Bispecific Antibodies via mRNA-LNPs Synergistically Suppresses Gastric Cancer Peritoneal Metastasis Through T Cell Co-Activation.International journal of nanomedicine · 2026Article
- Macrophage-Based Nanoplatforms for Tumor-Targeted Drug Delivery and Cancer Immunomodulation: Extracellular Vesicles, Membrane-Coated Nanoparticles, and Live Cells.International journal of nanomedicine · 2026Review
- Therapeutic mRNA vaccines for lung cancer: reshaping the tumor microenvironment to enhance anti-tumor immunity.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Nucleic acid-encoded antibody gene transfer-next generation of antibody therapies.Drug delivery · 2025Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Liver malignancies are among the tumor types that are resistant to immune checkpoint inhibition therapy. Tumor-associated macrophages (TAMs) are highly enriched and play a major role in inducing immunosuppression in liver malignancies. Herein, CCL2 and CCL5 are screened as two major chemokines responsible for attracting TAM infiltration and inducing their polarization toward cancer-promoting M2-phenotype. To reverse this immunosuppressive process, an innovative single-domain antibody that bispecifically binds and neutralizes CCL2 and CCL5 (BisCCL2/5i) with high potency and specificity is directly evolved. mRNA encoding BisCCL2/5i is encapsulated in a clinically approved lipid nanoparticle platform, resulting in a liver-homing biomaterial that allows transient yet efficient expression of BisCCL2/5i in the diseased organ in a multiple dosage manner. This BisCCL2/5i mRNA nanoplatform significantly induces the polarization of TAMs toward the antitumoral M1 phenotype and reduces immunosuppression in the tumor microenvironment. The combination of BisCCL2/5i with PD-1 ligand inhibitor (PD-Li) achieves long-term survival in mouse models of primary liver cancer and liver metastasis of colorectal and pancreatic cancers. The work provides an effective bispecific targeting strategy that could broaden the PD-Li therapy to multiple types of malignancies in the human liver.
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Registered trials
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.