ArticleOncogene2026
Dual-target CAR-T therapy for ovarian cancer: synergistic targeting of MSLN and B7H3 enhances anti-tumor efficacy and overcomes antigen heterogeneity.
Article in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Dual-Target Nectin-4/FAP Heterobivalent ProbeAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies.Cancers · 2026Review
- Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.Journal of ovarian research · 2026Review
- Receptor Co‑targeting Strategies for Personalized Ovarian Cancer Therapy.International journal of nanomedicine · 2026Review
- Genomic characterization of rabies virus glycoprotein co-expressing CD70 CAR-T cells during killing of glioma cellsFrontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer (OC) remains a lethal malignancy with limited treatment options owing to antigen heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, we designed a unique chimeric Antigen Receptor T-Cell (CAR-T) construct (B4M3) that integrates an anti-MSLN scFv linked to the CD3ζ activation domain and an anti-B7H3 scFv linked to the 4-1BB co-stimulatory domain. In vitro, B4M3 CAR-T cells exhibited robust cytotoxicity against OC cell lines with enhanced degranulation (CD107a) and efficient tumor cell killing, even at low effector-to-target ratios. In vivo, B4M3 CAR-T cells significantly inhibited tumor growth and prolonged survival and demonstrated superior tumor infiltration and persistence in OC xenograft models. Imaging mass cytometry (IMC) revealed that B4M3 treatment reshaped the TME, increased cytotoxic T lymphocyte (CTL) infiltration, and reduced regulatory T cells (Tregs). Mechanistically, B4M3 therapy upregulated TGF-β, promoting Th17 differentiation and CTL recruitment, thereby enhancing anti-tumor immunity. Our findings demonstrate that B4M3 CAR-T cells effectively address antigen heterogeneity and enhance therapeutic efficacy in OC, thereby offering a promising strategy for solid tumor immunotherapy.
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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.