ArticleNature cancer2023
Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors.
Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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
68 citing papers in PubMed, 74 citations in OpenAlex.
- Review
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- Stimuli-responsive structural transformation of adaptive peptide nanomaterials toward biomedical applications.Materials today. Bio · 2026Review
- Neutrophil-integrated syncytial CAR macrophage for cancer immunotherapy.Nature immunology · 2026Article
- A Drug-Gated, Modular STAb-T Immunotherapy With External Control.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chemically Masked aPD-L1-Sialidase Conjugate for Tumor-Specific Desialylation and Immunotherapy.Angewandte Chemie (International ed. in English) · 2026Article
- Cancer-associated alterations in O-GalNAc glycosylation.Glycobiology · 2026Review
- From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.Antibody therapeutics · 2026Review
- B7 homolog 3-targeted CAR-T cells secreting EGFR T-cell engagers for improved control of glioblastoma progression.Molecular biomedicine · 2026Article
- Engineering a conditionally active cetuximab prodrug via affibody-based paratope masking.Journal of biological engineering · 2026Article
- Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Peptide-protein docking: from physics-based models to generative intelligence.Chemical communications (Cambridge, England) · 2026Review
- Landscape of T-cell engagers in solid tumors.The oncologist · 2026Review
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- A trispecific antibody engaging T cells with tumour and myeloid cells augments antitumour immunity.Nature biomedical engineering · 2026Article
- Review
- Review
- Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.
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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.