ArticleToxins2015
Mutagenic Deimmunization of Diphtheria Toxin for Use in Biologic Drug Development.
Article in Toxins, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed.
- Enzyme-mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors.Bioengineering & translational medicine · 2026Review
- Clinically approved immunotoxins targeting hematological cancers: "the best of both worlds".Frontiers in pharmacology · 2025Review
- An enhanced intracellular delivery platform based on a distant diphtheria toxin homolog that evades pre-existing antitoxin antibodies.EMBO molecular medicine · 2024Article
- Potent and selective eradication of tumor cells by an EpCAM-targeted Ras-degrading enzyme.Molecular therapy oncolytics · 2023Article
- Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience.Toxins · 2022Review
- Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology.International journal of molecular sciences · 2021Review
- Antibody Conjugates for Targeted Therapy Against HIV-1 as an Emerging Tool for HIV-1 Cure.Frontiers in immunology · 2021Review
- Combinatorial Resurfacing of Dengue Envelope Protein Domain III Antigens Selectively Ablates Epitopes Associated with Serotype-Specific or Infection-Enhancing Antibody Responses.ACS combinatorial science · 2020Article
- A High-Throughput Single-Clone Phage Fluorescence Microwell Immunoassay and Laser-Driven Clonal Retrieval System.Biomolecules · 2020Article
- Immunogenicity of Immunotoxins ContainingFrontiers in immunology · 2020Review
- Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery.Biomaterials · 2019Article
- Hosts for Hostile Protein Production: The Challenge of Recombinant Immunotoxin Expression.Biomedicines · 2019Review
- Targeted Diphtheria Toxin-Based Therapy: A Review Article.Frontiers in microbiology · 2019Review
- Immunotoxins Targeting B cell Malignancy-Progress and Problems With Immunogenicity.Biomedicines · 2018Review
- Development of a Deimmunized Bispecific Immunotoxin dDT2219 against B-Cell Malignancies.Toxins · 2018Article
- Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity.Immunology · 2018Article
- Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Demmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins.Biomedicines · 2017Review
- Rational design of low immunogenic anti CD25 recombinant immunotoxin for T cell malignancies by elimination of T cell epitopes in PE38.Cellular immunology · 2017Article
- Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges.BioMed research international · 2017Review
- Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions.Biomaterials · 2016Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundTargeted toxins require multiple treatments and therefore must be deimmunized. We report a method of protein deimmunization based on the point mutation of highly hydrophilic R, K, D, E, and Q amino acids on the molecular surface of truncated diphtheria-toxin (DT390).
methodsBased on their surface position derived from an X-ray-crystallographic model, residues were chosen for point mutation that were located in prominent positions on the molecular surface and away from the catalytic site. Mice were immunized with a targeted toxin containing either a mutated DT390 containing seven critical point mutations or the non-mutated parental toxin form.
resultsSerum analysis revealed a significant 90% reduction in anti-toxin antibodies in mice immunized with the mutant, but not the parental drug form despite multiple immunizations. The experiment was repeated in a second strain of mice with a different MHC-haplotype to address whether point mutation removed T or B cell epitopes. Findings were identical indicating that B cell epitopes were eliminated from DT. The mutant drug form lost only minimal activity in vitro as well as in vivo.
conclusionThese findings indicate that this method may be effective for deimmunizing of other proteins and that discovery of a deimmunized form of DT may lead to the development of more effective targeted toxin.
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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.