ArticleJCI insight2024
Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Activation of an adaptive antitumor immune response by the polymeric fluoropyrimidine CF10 involves TS/Top1 dual targeting.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Artificial intelligence driven protein design and sustainable nanomedicine for advanced theranostics.Bioactive materials · 2026Review
- SAKE-PP: A Spatial-Attention Equivariant Network for Accurate Ranking of Protein-Protein Interaction Models.JACS Au · 2026Article
- Rewiring tumor cytokine networks to enhance immune checkpoint blockade: mechanisms, engineering, and clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Advances in IL-2 Family Cytokine-Based Cancer Therapies: Overcoming Challenges Through Molecular Engineering and Delivery Strategies.Immune network · 2026Review
- Immune checkpoint biology in hepatocellular carcinoma (Review).Oncology letters · 2025Review
- Dynamics and variegation in the Treg response to Interleukin-2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion.Journal for immunotherapy of cancer · 2025Article
- IL-7 Immunotherapies: Current Applications and Engineering Opportunities.Immunological investigations · 2025Review
- AnScience immunology · 2025Article
- An engineered Treg selective immunocytokine induces sustained immune modulation in a preclinical model of hemophilia A.Journal of thrombosis and haemostasis : JTH · 2025Article
- [Biological activity and antitumor effect of long-acting recombinant human interleukin-2 drug].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Cytokine/Antibody Fusion Protein Design and Evaluation.Current protocols · 2024Article
- An engineered immunocytokine with collagen affinity improves the tumor bioavailability, tolerability, and therapeutic efficacy of IL-2.Cell reports. Medicine · 2023Article
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21 authors.
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Abstract
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both pro-inflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum half-life. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.
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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.