ArticleThe Journal of experimental medicine2022
An engineered concealed IL-15-R elicits tumor-specific CD8+T cell responses through PD-1-cis delivery.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Breaking barriers in gynecologic malignancies with adoptive cell transfers and nanomedicine.Cell biomaterials · 2026Article
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Stroma-specific IL-15 coordinates epithelial IL-15Rα to promote intestinal epithelial repair.Science China. Life sciences · 2026Article
- Tumor-infiltrating lymphocytes demonstrate potent anti-tumor efficacy and synergize with PD-1 blockade in bladder cancer.Journal of translational medicine · 2026Article
- An innovative engineered IL-10 monomer strengthens T cell-mediated anti-tumor responses through anti-PD-1 cis-delivery.Cell reports. Medicine · 2026Article
- Stem-like T cells in cancer immunotherapy: biology, regulation and therapeutic targeting.Frontiers in immunology · 2026Review
- A new strategy for CAR-T therapy in solid tumors: IL-15-autocrine signaling augments tumor stroma depletion and promotes a TCell death & disease · 2025Article
- Pre-Treatment with Dacarbazine Sensitizes B16 Melanoma to CAR T Cell Therapy in Syngeneic Mouse Model.International journal of molecular sciences · 2025Article
- TGF-βRII/IL-15 immunotherapeutic complex targets exhausted CD8Journal for immunotherapy of cancer · 2025Article
- Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- Novel fusion superkine,Journal for immunotherapy of cancer · 2025Article
- Concurrent intratumoural TNature biomedical engineering · 2025Article
- Novel PD-1-targeted, activity-optimized IL-15 mutein SOT201 acting in cis provides antitumor activity superior to PD1-IL2v.Journal for immunotherapy of cancer · 2025Article
- IL-15: from discovery to FDA approval.Journal of hematology & oncology · 2025Article
- Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21.Frontiers in immunology · 2025Article
- AWT020: a novel fusion protein harnessing PD-1 blockade and selective IL-2 Cis-activation for enhanced anti-tumor immunity and diminished toxicity.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Checkpoint blockade immunotherapy releases the inhibition of tumor-infiltrating lymphocytes (TILs) but weakly induces TIL proliferation. Exogenous IL-15 could further expand TILs and thus synergize with αPD-L1 therapy. However, systemic delivery of IL-15 extensively expands peripheral NK cells, causing severe toxicity. To redirect IL-15 to intratumoral PD-1+CD8+T effector cells instead of NK cells for better tumor control and lower toxicity, we engineered an anti-PD-1 fusion with IL-15-IL-15Rα, whose activity was geographically concealed by immunoglobulin Fc region with an engineered linker (αPD-1-IL-15-R) to bypass systemic NK cells. Systematic administration of αPD-1-IL-15-R elicited extraordinary antitumor efficacy with undetectable toxicity. Mechanistically, cis-delivery of αPD-1-IL-15-R vastly expands tumor-specific CD8+T cells for tumor rejection. Additionally, αPD-1-IL-15-R upregulated PD-1 and IL-15Rβ on T cells to create a feedforward activation loop, thus rejuvenating TILs, not only resulting in tumor control in situ, but also suppressing tumor metastasis. Collectively, renavigating IL-15 to tumor-specific PD-1+CD8+T cells, αPD-1-IL-15-R elicits effective systemic antitumor immunity.
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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.