ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
A bispecific antibody targeting GPC3 and CD47 induced enhanced antitumor efficacy against dual antigen-expressing HCC.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 96 citations in OpenAlex.
- Development of a novel immune infiltration-based gene signature to predict prognosis and immunotherapy response of a novel anti-PD-L1/TGF-β bifunctional fusion protein in recurrent cervical cancer.Human vaccines & immunotherapeutics · 2026Article
- An IgG-like fusion protein comprising an anti-spike S2 antibody and ACE2 exhibits potent and broad neutralization against SARS-CoV-2 and variants of concern.Antibody therapeutics · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Glypican-3-targeted therapy in hepatocellular carcinoma: biological insights and therapeutic strategies.Cancer gene therapy · 2026Review
- Contrast-enhanced ultrasound and clinical features for preoperative prediction of GPC-3 expression in hepatocellular carcinoma.Abdominal radiology (New York) · 2026Article
- Emerging Immune-Based Therapeutic Strategies in Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Immune-mediated tumor regression and subsequent escape driven by antigen loss and major histocompatibility complex (MHC) class I downregulation following GPC3 DNA vaccination in hepatocellular carcinoma.Hepatobiliary surgery and nutrition · 2026Article
- Noninvasive prediction of glypican-3 expression and recurrence-free survival in hepatocellular carcinoma using contrast-enhanced ultrasound.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Article
- Efficacy and safety of approved cellular therapies and bispecific antibodies in solid tumors: the current state.Discover oncology · 2026Review
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Therapeutic Strategies for Hepatocellular Carcinoma: Current Advances and Future Perspectives.Vaccines · 2026Review
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- Research on Anti-tumor Pharmacodynamics of Multi-functional Magnetic Lipid Polymer with Specific Targeted Transmission of siRNA and its Toxicity Evaluation.Current pharmaceutical design · 2026Article
- Targeting CD47-mediated cancer senescence, a novel strategy for cancer immunotherapy.Frontiers in immunology · 2026Review
- Rewiring tumor-associated macrophages in hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glypican-3 (GPC3) is a well-characterized hepatocellular carcinoma (HCC)-associated antigen, yet anti-GPC3 therapies have achieved only minimal clinical progress. CD47 is a ubiquitously expressed innate immune checkpoint that promotes evasion of tumors from immune surveillance. Given both the specific expression of GPC3 in HCC and the known phagocytosis inhibitory effect of CD47 in liver cancer, we hypothesized that a bispecific antibody (BsAb) that co-engages with GPC3 and CD47 may offer excellent antitumor efficacy with minimal toxicity. Here, we generated a novel BsAb: GPC3/CD47 biAb. With the use of both in vitro and in vivo assays, we found that GPC3/CD47 biAb exerts strong antitumor activity preferentially against dual antigen-expressing tumor cells. In hCD47/human signal regulatory protein alpha (hCD47/hSIRPα) humanized mice, GPC3/CD47 biAb had an extended serum half-life without causing systemic toxicity. Importantly, GPC3/CD47 biAb induced enhanced Fc-mediated effector functions to dual antigen-expressing HCC cells in vitro, and both macrophages and neutrophils are required for its strong efficacy against xenograft HCC tumors. Notably, GPC3/CD47 biAb outperformed monotherapies and a combination therapy with anti-CD47 and anti-GPC3 monoclonal antibodies (mAbs) in a xenograft HCC model. Our study illustrates a strategy for improving HCC treatment by boosting innate immune responses and presents new insights to inform antibody design for the future development of innovative immune therapies.
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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.