ArticleJournal for immunotherapy of cancer2025
Overcoming immunotherapy resistance in bladder cancer with a novel antibody-drug conjugate RC48.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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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
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The efficacy and safety of disitamab vedotin plus immunotherapy in locally advanced or metastatic solid tumors: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- TROPION-Urothelial03: a phase II/III study of datopotamab deruxtecan (Dato-DXd) for locally advanced or metastatic urothelial carcinoma.Future oncology (London, England) · 2026Trial
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Radiomics and deep learning fusion model based on multiphasic CT for predicting HER2 expression status in bladder urothelial carcinoma: a multicenter study.Translational andrology and urology · 2026Article
- Immunotherapy role in bladder cancer treatment: a review of literature.Frontiers in oncology · 2026Review
- Recent advances in immunotherapy for bladder cancer: mechanisms, clinical applications, and future perspectives.Frontiers in oncology · 2026Review
- Disitamab vedotin (RC48-ADC) combined with immunotherapy as neoadjuvant therapy for localized muscle-invasive bladder cancer: a multicenter real-world study.NPJ precision oncology · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors have shown limited response rates in bladder cancer. RC48-antibody-drug conjugate (ADC) shows potential for combination with immune checkpoint inhibitors. This study aimed to elucidate RC48-ADC's mechanism in sensitizing tumors to immunotherapy and identify optimal combination strategies.
methodsBioinformatics (The Cancer Genome Atlas, GEO, Xiangya cohorts) analyzed correlations between HER2, immune markers, and therapy response. The h-HER2-MB49 and sg-PD-L1-MB49 cell line was generated. In vitro/vivo models assessed RC48-ADC's impact on the tumor immune microenvironment using flow cytometry, immunofluorescence, co-culture, chemotaxis, CUT&Tag assays, transcriptomics, and ELISA. Subcutaneous tumor models evaluated combination therapies. At the clinical level, bladder cancer immune therapy cohort tissue microarrays were used, and the aforementioned mechanisms were validated using immunohistochemistry and immunofluorescence.
resultsHER2 expression is associated with an inhibitory tumor immune microenvironment and resistance to immunotherapy. RC48-ADC treatment can reactivate this HER2-related inhibitory tumor immune microenvironment, thereby enhancing immunotherapy effectiveness. Mechanistically, RC48-ADC reactivates the tumor immune microenvironment by reducing PD-L1 transcription via Hippo pathway activation. It also promotes the release of chemokines (CCL5, CXCL9, and CXCL14) and recruits cytotoxic T-lymphocytes. In preclinical mouse models, RC48-ADC synergized with CTLA-4 and PD-L1 antibodies.
conclusionsRC48-ADC enhances immunotherapy by regulating PD-L1 through the Hippo-TAZ pathway and reactivating CD8+T cells, offering a novel combination therapeutic strategy for bladder cancer.
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