ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- A Potent Single-Domain Antibody Targeting LAG-3 for Efficient Tumor Immunotherapy.Current issues in molecular biology · 2026Article
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Overcoming immune resistance in hepatocellular carcinoma: insights into mechanisms, predictive factors, and interventional strategies.Frontiers in immunology · 2026Review
- Phase 1 study evaluating the safety, preliminary efficacy, and pharmacodynamics of recombinant interleukin-15 in combination with nivolumab and ipilimumab in patients with refractory cancers.Journal for immunotherapy of cancer · 2025Article
- IL-15 signaling via cis- and trans-presentation to progenitor-exhausted CD8Journal of nanobiotechnology · 2025Article
- Transient Receptor Potential Melastatin 4 (TRPM4) is associated with an immuno-stimulatory TME and better prognosis in BLCA.Discover oncology · 2025Article
- Nanobody-engineered bispecific IL-18 mimetics drive antitumor immunity by engaging CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Universal Fab-Fc masked cytokine prodrug platform: αPD-L1/IL-15 prodrug activates CD44Journal for immunotherapy of cancer · 2025Article
- Emerging nanocarriers designed for the enhanced delivery of doxorubicin.Nanomedicine (London, England) · 2025Review
- EngineeredJournal for immunotherapy of cancer · 2025Article
- Advances in Antibody-Based Immune-Stimulating Drugs: Driving Innovation in Cancer Therapy.International journal of molecular sciences · 2025Review
- Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity.PloS one · 2025Article
- IL-2 and IL-15 augment HBV therapeutic vaccination and PD1 blockade for functional cure in the AAV-HBV mouse model.Frontiers in immunology · 2025Article
- A tumor-conditional IL-15 safely synergizes with immunotherapy to enhance antitumor immune responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Cellular mechanisms of combining innate immunity activation with PD-1/PD-L1 blockade in treatment of colorectal cancer.Molecular cancer · 2024Review
- Advancements and challenges in immunocytokines: A new arsenal against cancer.Acta pharmaceutica Sinica. B · 2024Review
- Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity.Cell reports. Medicine · 2024Article
- Immunotherapy for colorectal cancer: insight from inherited genetics.Trends in cancer · 2024Review
- Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.Immunological reviews · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the demonstrated immense potential of immune checkpoint inhibitors in various types of cancers, only a minority of patients respond to these therapies. Immunocytokines designed to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME) and block the immune checkpoint simultaneously may provide a strategic advantage over the combination of two single agents. To increase the response rate to checkpoint blockade, in this study, we developed a novel immunocytokine (LH01) composed of the antibody against programmed death-ligand 1 (PD-L1) fused to interleukin (IL)-15 receptor alpha-sushi domain/IL-15 complex. We demonstrate that LH01 efficiently binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. In syngeneic mouse models, LH01 showed improved antitumor efficacy and safety versus anti-PD-L1 plus LH02 (Fc-sushi-IL15) combination and overcame resistance to anti-PD-L1 treatment. Mechanistically, the dual anti-immunosuppressive function of LH01 activated both the innate and adaptive immune responses and induced a favorable and immunostimulatory TME. Furthermore, combination therapy with LH01 and bevacizumab exerts synergistic antitumor effects in an HT29 colorectal xenograft model. Collectively, our results provide supporting evidence that fusion of anti-PD-L1 and IL-15 might be a potent strategy to treat patients with cold tumors or resistance to checkpoint blockade.
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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.