ArticleJournal of nanobiotechnology2025
Advancing liver cancer treatment with dual-targeting CAR-T therapy.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Immune-modified exosome vaccine loaded with liver cancer epitope peptides induces potent and specific antitumor immunity.Journal of nanobiotechnology · 2026Article
- <p>Converting 'cold' to 'hot' hepatocellular carcinoma for improved immunotherapy (Review)</p>.Molecular medicine reports · 2026Review
- Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies.World journal of clinical oncology · 2026Review
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Immune crosstalk in metabolic dysfunction-associated steatotic liver disease: interactions between innate and adaptive immunity.Frontiers in immunology · 2026Review
- Nanotechnology-Enabled Diagnosis and Treatment of Hepatocellular Carcinoma: Theranostics, Combination Regimens, and Translation.International journal of nanomedicine · 2026Review
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- Advancing breast cancer treatment through dual targeting CAR T cell therapy.Discover oncology · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cell therapy targeting glypican-3 (GPC3) has shown promise in the treatment of hepatocellular carcinoma (HCC). However, the efficacy of CAR-T cells that focus solely on cell surface tumor-associated antigens is often limited. To overcome this challenge, we developed a dual-targeting CAR-T cell strategy. The intracellular alpha-fetoprotein (AFP) antigen, a well-established biomarker of liver cancer, presents the immunogenic Human Leukocyte Antigen (HLA)-A*02:01-restricted epitope 158-166. Consequently, we engineered a T cell receptor (TCR) mimic antibody with high specificity and affinity, providing a promising therapeutic avenue to target this critical antigen. To enhance treatment outcomes for liver cancer, we further modified previously developed GPC3 CAR-T cells, which demonstrated robust anti-tumor efficacy against GPC3-high tumor cells, to secrete an optimized bispecific T cell engager (BiTE) targeting the presented AFP antigen. This dual-targeting strategy significantly improved CAR-T cell proliferation and persistence, as well as enhancing cytokine expression and anti-tumor activity against HCC cells, particularly those exhibiting low GPC3 and AFP expression, both in vitro and in vivo. Our findings highlight the potential of this innovative approach to offer more effective treatment options for patients with liver cancer.
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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.