ArticleCellular & molecular immunology2017
Elimination of murine and human T-cell epitopes in recombinant immunotoxin eliminates neutralizing and anti-drug antibodies in vivo.
Article in Cellular & molecular immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Review
- Integrated computational and experimental immunoengineering of adeno-associated virus capsid T cell epitopes in mice.Nature communications · 2026Article
- Evaluation of the Safety of A Novel Anti-HER2 Immunotoxin Containing Modified Fragment ofIranian journal of biotechnology · 2025Article
- A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived fromFrontiers in veterinary science · 2025Article
- Robust genome and cell engineering via in vitro and in situ circularized RNAs.Nature biomedical engineering · 2025Article
- Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics.Nature reviews. Drug discovery · 2024Review
- Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes.Toxins · 2023Review
- Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms.Bioengineering (Basel, Switzerland) · 2023Review
- Design and construction of scFv-PE35KDEL as a novel immunotoxin against human epidermal growth factor receptor 2 for cancer therapy.Biotechnology letters · 2023Article
- Article
- Review
- Development of Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer: An Update.Biomolecules · 2020Review
- Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention.Hepatology (Baltimore, Md.) · 2020Article
- Blockade of IGF2R improves muscle regeneration and ameliorates Duchenne muscular dystrophy.EMBO molecular medicine · 2020Article
- Immunogenicity of Protein Therapeutics: A Lymph Node Perspective.Frontiers in immunology · 2020Review
- Article
- Immunogenicity of Immunotoxins ContainingFrontiers in immunology · 2020Review
- Deimmunizing substitutions inThe Journal of biological chemistry · 2019Article
- Anti-drug antibodies to LMB-100 are enhanced by mAbs targeting OX40 and CTLA4 but not by mAbs targeting PD1 or PDL-1.Cellular immunology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Antibodies against the toxin portion of recombinant immunotoxins (RIT) reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SS1P to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SS1P modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies (ADA), whereas mice immunized with SS1P, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.
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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.