ArticleJournal for immunotherapy of cancer2025
A bispecific antibody targeting PD-L1/TNFR2 increases tumor targeting and enhances antitumor efficacy in colorectal cancer.
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 6 papers.
What it found
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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
6 citing papers in PubMed.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Clinical trials of bispecific antibody therapy for colorectal cancer: advanced and next steps.Frontiers in oncology · 2026Review
- Antibody targeting of the TNF-TNFR2 axis to overcome tumor immune resistance.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors (ICIs) have shown limited efficacy in colorectal cancer (CRC), largely due to immunosuppressive tumor microenvironment (TME) including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Additionally, the off-target effects of ICIs can reduce drug accumulation in tumor tissues and lead to immune-related adverse events, further compromising their clinical utility.
methodsUsing knob-into-hole technology, we developed ATAPL1, a bispecific antibody targeting both programmed death-ligand 1 (PD-L1) and tumor necrosis factor receptor 2 (TNFR2). In multiple subcutaneous and orthotopic CRC mouse models, ATAPL1 was evaluated for its tumor targeting, antitumor efficacy, immunomodulatory effects within the TME, and potential combinations with standard chemotherapies.
resultsCompared with αPD-L1 or αTNFR2 monotherapy, ATAPL1 showed enhanced tumor accumulation and significantly improved antitumor efficacy, with no significant toxicity. It effectively modulated the TME by decreasing immunosuppressive Tregs and monocytic MDSCs (M-MDSCs), while promoting CD8
conclusionThese findings support ATAPL1 as a promising dual-targeted therapeutic strategy for CRC. It offers the potential to overcome immune and chemotherapy resistance, reduce off-target effects, and improve treatment outcomes through enhanced immune activation and tumor targeting.
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