ArticlePNAS nexus2022
Intratumoral nanobody-IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice.
Article in PNAS nexus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.Frontiers in immunology · 2023Pooled it
- Article
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Identification of Pancreatic Ductal Adenocarcinoma Extracellular Matrix Signatures from In-Depth Proteomic Profiling that Correlate with Lymphocyte Infiltration.Cancer research communications · 2026Article
- Biochemical signals from the extracellular matrix in inflammation and tumour immunology.Nature reviews. Immunology · 2026Review
- Engineering hyaluronic acid-binding cytokines for enhanced tumor retention and safety.bioRxiv : the preprint server for biology · 2026Article
- The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.Nature reviews. Urology · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Nanobodies in biomedicine: from molecular characteristics to fabrication and clinical translation.Military Medical Research · 2026Review
- Targeting angiogenesis: advances in the design and engineered applications of nanobodies.Frontiers in immunology · 2026Review
- Nanobody Therapeutics in Alzheimer's Disease: From Molecular Mechanisms to Translational Approaches.Antibodies (Basel, Switzerland) · 2025Review
- Application of nanobody‑based CAR‑T in tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- In Situ Vaccines in the Era of Cancer Immunotherapy: Conceptual Innovation and Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Combinatorial treatment with upadacitinib abrogates systemic toxicity of a tumor-targeted IL-2 fusion protein.Journal for immunotherapy of cancer · 2025Article
- Advances in Therapeutic Cancer Vaccines, Their Obstacles, and Prospects Toward Tumor Immunotherapy.Molecular biotechnology · 2025Review
- Review
- Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024Review
- Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.Journal of nanobiotechnology · 2024Review
- CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity.Cancer immunology research · 2024Article
- Therapeutic cancer vaccines: advancements, challenges, and prospects.Signal transduction and targeted therapy · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Confining cytokine exposure to the tumors would greatly enhance cancer immunotherapy safety and efficacy. Immunocytokines, cytokines fused to tumor-targeting antibodies, have been developed with this intention, but without significant clinical success to date. A critical limitation is uptake by receptor-expressing cells in the blood, that decreases the dose at the tumor and engenders toxicity. Small-format immunocytokines, constructed with antibody fragments, are hypothesized to improve tumor specificity due to rapid systemic clearance. However, effective design criteria for small-format immunocytokines need further examination. Here, we engineer small interleukin-2 (IL-2) immunocytokines fused to nanobodies with nanomolar to picomolar affinities for the tumor-specific EIIIB domain of fibronectin (also known as EDB). Upon intravenous delivery into immunocompetent mice, such immunocytokines led to similar tumor growth delay as size-matched untargeted IL-2. Intratumoral (i.t.) delivery imparted improved survival dependent on affinity to EIIIB. I.t. administration offers a promising avenue to deliver small-format immunocytokines, given effective affinity for the tumor microenvironment.
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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.