ArticleNature communications2021
A cytokine receptor-masked IL2 prodrug selectively activates tumor-infiltrating lymphocytes for potent antitumor therapy.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
75 citing papers in PubMed, 112 citations in OpenAlex.
- De novo design of protease-activatable cytokine prodrugs.bioRxiv : the preprint server for biology · 2026Article
- A Tumor-Microenvironment-Responsive Chemically Masked IL‑2 Prodrug Potentiates PD‑1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy.ACS central science · 2026Article
- Chemically Masked aPD-L1-Sialidase Conjugate for Tumor-Specific Desialylation and Immunotherapy.Angewandte Chemie (International ed. in English) · 2026Article
- Mesoporous polydopamine nanoplatform enhances IL-2 immunotherapy for hepatocellular carcinoma via mild photothermal therapy and lactate regulation.Asian journal of pharmaceutical sciences · 2026Article
- Programmed Cell Death Protein 1-Interleukin-2 Bispecific Agents for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Timosaponin AIII enhances CAR-T cell potency and prevents relapse through impairing CAR-Tregs.Nature communications · 2026Article
- Advances in IL-2 Family Cytokine-Based Cancer Therapies: Overcoming Challenges Through Molecular Engineering and Delivery Strategies.Immune network · 2026Review
- Targeting severe acidity for tumor-activatable Interleukin-2 therapy.Cell reports. Medicine · 2026Article
- Advances in IL-2-based cancer immunotherapy and the synergistic role of stem-like CD8Frontiers in immunology · 2026Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- Orthogonalized human protease control of secreted signals.Nature chemical biology · 2025Article
- Tumor infiltration therapy: from FDA approval to next-generation approaches.Clinical and experimental medicine · 2025Review
- Article
- In vitro and in vivo evaluation of chemically synthesized, receptor-biased interleukin-4 and photocaged variants.Science advances · 2025Article
- Engineering high-efficiency matriptase substrates using E. coli display for applications in prodrug activation.Cell reports methods · 2025Article
- TIM3-blockade synergizes with IL2 in alleviating intra-tumoral CD8Nature communications · 2025Article
- Conditional Activation of Protein Therapeutics by Templated Removal of Peptide Nucleic Acid Masking Groups.Angewandte Chemie (International ed. in English) · 2025Article
- Novel anti-CD73-IL-2v bispecific fusion protein augments antitumor immunity by alleviating immunosuppressive adenosine pathways in CD8Journal for immunotherapy of cancer · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
As a potent lymphocyte activator, interleukin-2 (IL-2) is an FDA-approved treatment for multiple metastatic cancers. However, its clinical use is limited by short half-life, low potency, and severe in vivo toxicity. Current IL-2 engineering strategies exhibit evidence of peripheral cytotoxicity. Here, we address these issues by engineering an IL-2 prodrug (ProIL2). We mask the activity of a CD8 T cell-preferential IL-2 mutein/Fc fusion protein with IL2 receptor beta linked to a tumor-associated protease substrate. ProIL2 restores activity after cleavage by tumor-associated enzymes, and preferentially activates inside tumors, where it expands antigen-specific CD8 T cells. This significantly reduces IL-2 toxicity and mortality without compromising antitumor efficacy. ProIL2 also overcomes resistance of cancers to immune checkpoint blockade. Lastly, neoadjuvant ProIL2 treatment can eliminate metastatic cancer through an abscopal effect. Taken together, our approach presents an effective tumor targeting therapy with reduced toxicity.
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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.