ArticleNature biomedical engineering2022
Masking the immunotoxicity of interleukin-12 by fusing it with a domain of its receptor via a tumour-protease-cleavable linker.
Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.Cancer biology & therapy · 2026Review
- Controllable gene delivery via masked adeno-associated viral vectors.Nature materials · 2026Article
- De novo design of protease-activatable cytokine prodrugs.bioRxiv : the preprint server for biology · 2026Article
- αHSA-proIL-12: A Tumor-Conditional IL-12 Prodrug with Reduced Systemic Toxicity and Potent Antitumor Activity.International journal of molecular sciences · 2026Article
- Data-centric feedback loops for next-generation immunotherapy development.Nature biomedical engineering · 2026Review
- 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
- Development of bicistronic plasmids and fusion proteins for clinical translation of tumor immune reprogramming.Molecular therapy. Advances · 2026Article
- ProNotch converts extracellular protease activity into programmable transcriptional outputs.bioRxiv : the preprint server for biology · 2026Article
- Interleukin 12-tethered nano-aluminum adjuvant orchestrates environmental immunomodulation to empower cytotoxic T cells against solid tumors.Acta pharmaceutica Sinica. B · 2026Article
- From Neoantigens to Nanocarriers: Modern Methods and Modalities in Using Peptides for Cancer Vaccination.Biochemistry · 2026Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- Natural and Engineered Cytokines as Cancer Therapeutics.Annual review of cancer biology · 2026Article
- A low-toxicity circular single-stranded DNA platform for safe and potent IL-12 immunotherapy against hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
- Advances in IL-2 Family Cytokine-Based Cancer Therapies: Overcoming Challenges Through Molecular Engineering and Delivery Strategies.Immune network · 2026Review
- IL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer.Nature materials · 2026Article
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Spatial multiomics to inform immunocytokine engineering: knowledge base, gaps, and QC solutions.Frontiers in immunology · 2026Review
- Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models.Oncoimmunology · 2025Article
- Nanotechnology-enhanced immunotherapies for pancreatic ductal adenocarcinoma: challenges and opportunities.Drug delivery and translational research · 2025Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 2 countries.
Funding
Abstract
Immune-checkpoint inhibitors have shown modest efficacy against immunologically 'cold' tumours. Interleukin-12 (IL-12)-a cytokine that promotes the recruitment of immune cells into tumours as well as immune cell activation, also in cold tumours-can cause severe immune-related adverse events in patients. Here, by exploiting the preferential overexpression of proteases in tumours, we show that fusing a domain of the IL-12 receptor to IL-12 via a linker cleavable by tumour-associated proteases largely restricts the pro-inflammatory effects of IL-12 to tumour sites. In mouse models of subcutaneous adenocarcinoma and orthotopic melanoma, masked IL-12 delivered intravenously did not cause systemic IL-12 signalling and eliminated systemic immune-related adverse events, led to potent therapeutic effects via the remodelling of the immune-suppressive microenvironment, and rendered cold tumours responsive to immune-checkpoint inhibition. We also show that masked IL-12 is activated in tumour lysates from patients. Protease-sensitive masking of potent yet toxic cytokines may facilitate their clinical translation.
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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.