ArticlePLoS biology2019
Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Tumor-associated protease-activated anti-CD47 antibody precisely maintains phagocytic ability of macrophages with minimal effect on healthy tissue.Journal of translational medicine · 2026Article
- Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Spatial-hindrance-based pro-Adalimumab prevents anti-idiotypic antibody interference in pharmacokinetic and therapeutic efficacy.Bioengineering & translational medicine · 2025Article
- Integrating molecular dynamics simulation with small- and wide-angle X-ray scattering to unravel the flexibility, antigen-blocking, and protease-restoring functions in a hindrance-based pro-antibody.Protein science : a publication of the Protein Society · 2024Article
- Article
- Article
- Cell-based therapies for the treatment of rheumatoid arthritis.Immunity, inflammation and disease · 2023Review
- A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.Inflammation and regeneration · 2023Article
- Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice.Nature communications · 2022Article
- Exploiting protease activation for therapy.Drug discovery today · 2022Review
- Identification of key candidate genes and biological pathways in the synovial tissue of patients with rheumatoid arthritis.Experimental and therapeutic medicine · 2022Article
- CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications.Biomedicines · 2022Review
- Hydrogels for the treatment of rheumatoid arthritis.Frontiers in bioengineering and biotechnology · 2022Review
- Development of a structure-based computational simulation to optimize the blocking efficacy of pro-antibodies.Chemical science · 2021Article
- Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy.Scientific reports · 2021Article
- The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control.ACS central science · 2021Review
- Function and Role of Regulatory T Cells in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy.Frontiers in immunology · 2021Article
- Modulating TNFα activity allows transgenic IL15-Expressing CLL-1 CAR T cells to safely eliminate acute myeloid leukemia.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During rheumatoid arthritis (RA) treatment, long-term injection of antitumor necrosis factor α antibodies (anti-TNFα Abs) may induce on-target toxicities, including severe infections (tuberculosis [TB] or septic arthritis) and malignancy. Here, we used an immunoglobulin G1 (IgG1) hinge as an Ab lock to cover the TNFα-binding site of Infliximab by linking it with matrix metalloproteinase (MMP) -2/9 substrate to generate pro-Infliximab that can be specifically activated in the RA region to enhance the selectivity and safety of treatment. The Ab lock significantly inhibits the TNFα binding and reduces the anti-idiotypic (anti-Id) Ab binding to pro-Infliximab by 395-fold, 108-fold compared with Infliximab, respectively, and MMP-2/9 can completely restore the TNFα neutralizing ability of pro-Infliximab to block TNFα downstream signaling. Pro-Infliximab was only selectively activated in the disease site (mouse paws) and presented similar pharmacokinetics (PKs) and bio-distribution to Infliximab. Furthermore, pro-Infliximab not only provided equivalent therapeutic efficacy to Infliximab but also maintained mouse immunity against Listeria infection in the RA mouse model, leading to a significantly higher survival rate (71%) than that of the Infliximab treatment group (0%). The high-selectivity pro-Infliximab maintains host immunity and keeps the original therapeutic efficiency, providing a novel strategy for RA therapy.
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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.