ArticleNature communications2020
Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 89 citations in OpenAlex.
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- 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
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- Pathological insights of human CD34+ hematopoietic stem cell-engrafted NSG mice: Implications for the safety assessment of cancer immunotherapy drugs.Veterinary pathology · 2026Article
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- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
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- T cell engagers: expanding horizons in oncology and beyond.British journal of cancer · 2025Review
- Single-chain Fab chain-exchange (scFab-PACE) converts targeted prodrugs into functional T cell engagers on tumor cells.The Journal of biological chemistry · 2025Article
- Targeting the tumour cell surface in advanced prostate cancer.Nature reviews. Urology · 2025Review
- Macrocyclic Phage Display for Identification of Selective Protease Substrates.Journal of the American Chemical Society · 2025Article
- Bispecific Antibodies in Solid Tumors: Advances and Challenges.International journal of molecular sciences · 2025Review
- CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Design of a prodrug bispecific antibody masked by a functional molecule for lymphocyte activation for cancer therapy.Journal of biological engineering · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell bispecific antibodies (TCBs) crosslink tumor and T-cells to induce tumor cell killing. While TCBs are very potent, on-target off-tumor toxicity remains a challenge when selecting targets. Here, we describe a protease-activated anti-folate receptor 1 TCB (Prot-FOLR1-TCB) equipped with an anti-idiotypic anti-CD3 mask connected to the anti-CD3 Fab through a tumor protease-cleavable linker. The potency of this Prot- FOLR1-TCB is recovered following protease-cleavage of the linker releasing the anti-idiotypic anti-CD3 scFv. In vivo, the Prot-FOLR1-TCB mediates antitumor efficacy comparable to the parental FOLR1-TCB whereas a noncleavable control Prot-FOLR1-TCB is inactive. In contrast, killing of bronchial epithelial and renal cortical cells with low FOLR1 expression is prevented compared to the parental FOLR1-TCB. The findings are confirmed for mesothelin as alternative tumor antigen. Thus, masking the anti-CD3 Fab fragment with an anti-idiotypic mask and cleavage of the mask by tumor-specific proteases can be applied to enhance specificity and safety of TCBs.
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