ArticleProceedings of the National Academy of Sciences of the United States of America2015
Antigen specificity can be irrelevant to immunocytokine efficacy and biodistribution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 119 citations in OpenAlex.
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- Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.Molecular cancer · 2026Review
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Anti-cancer immune priming with β-radioligand therapy using a novel high affinity antibody selectively targeting the 4Ig-Isoform of B7-H3.Theranostics · 2026Article
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Dual targeting OX40 and IL-2 receptor enhances antitumor activity through tumor-infiltrating Treg depletion and CD8Journal for immunotherapy of cancer · 2025Article
- Universal Fab-Fc masked cytokine prodrug platform: αPD-L1/IL-15 prodrug activates CD44Journal for immunotherapy of cancer · 2025Article
- Extracellular Vesicles as Precision Delivery Systems for Biopharmaceuticals: Innovations, Challenges, and Therapeutic Potential.Pharmaceutics · 2025Review
- 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
- CLEC12A-directed immunocytokine with target cell-restricted IL-15 activity for treatment of acute myeloid leukemia.Frontiers in immunology · 2025Article
- A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.Cell reports. Medicine · 2024Article
- Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity.Nature immunology · 2024Article
- CD45 threads the needle of cytokine cancer immunotherapy.Nature immunology · 2024Article
- CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity.Cancer immunology research · 2024Article
- High efficacy of huCD20-targeted AcTaferon in humanized patient derived xenograft models of aggressive B cell lymphoma.Experimental hematology & oncology · 2024Article
- Harnessing CD8 T cell responses using PD-1-IL-2 combination therapy.Trends in cancer · 2024Review
- Local delivery of cell surface-targeted immunocytokines programs systemic anti-tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- Tumor-Homing Antibody-Cytokine Fusions for Cancer Therapy.OncoTargets and therapy · 2024Review
- Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cytokine therapy can activate potent, sustained antitumor responses, but collateral toxicity often limits dosages. Although antibody-cytokine fusions (immunocytokines) have been designed with the intent to localize cytokine activity, systemic dose-limiting side effects are not fully ameliorated by attempted tumor targeting. Using the s.c. B16F10 melanoma model, we found that a nontoxic dose of IL-2 immunocytokine synergized with tumor-specific antibody to significantly enhance therapeutic outcomes compared with immunocytokine monotherapy, concomitant with increased tumor saturation and intratumoral cytokine responses. Examination of cell subset biodistribution showed that the immunocytokine associated mainly with IL-2R-expressing innate immune cells, with more bound immunocytokine present in systemic organs than the tumor microenvironment. More surprisingly, immunocytokine antigen specificity and Fcγ receptor interactions did not seem necessary for therapeutic efficacy or biodistribution patterns because immunocytokines with irrelevant specificity and/or inactive mutant Fc domains behaved similarly to tumor-specific immunocytokine. IL-2-IL-2R interactions, rather than antibody-antigen targeting, dictated immunocytokine localization; however, the lack of tumor targeting did not preclude successful antibody combination therapy. Mathematical modeling revealed immunocytokine size as another driver of antigen targeting efficiency. This work presents a safe, straightforward strategy for augmenting immunocytokine efficacy by supplementary antibody dosing and explores underappreciated factors that can subvert efforts to purposefully alter cytokine biodistribution.
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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.