ArticleBiotechnology and bioengineering2015
Protein deimmunization via structure-based design enables efficient epitope deletion at high mutational loads.
Article in Biotechnology and bioengineering, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Computational design and translational development of TCR-mimic scFv antibodies for peptide-HLA neoantigen targeting.npj drug discovery · 2026Review
- Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.Cell systems · 2025Article
- PITHA: A Webtool to Predict Immunogenicity for Humanized and Fully Human Therapeutic Antibodies.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy.Nature biomedical engineering · 2019Article
- Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity.BMC bioinformatics · 2019Article
- OSPREY 3.0: Open-source protein redesign for you, with powerful new features.Journal of computational chemistry · 2018Article
- Strategies to Reduce the Immunogenicity of Recombinant Immunotoxins.The American journal of pathology · 2018Review
- DisruPPI: structure-based computational redesign algorithm for protein binding disruption.Bioinformatics (Oxford, England) · 2018Article
- Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity.Immunology · 2018Article
- Article
- Computationally optimized deimmunization libraries yield highly mutated enzymes with low immunogenicity and enhanced activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- 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
- Elimination of murine and human T-cell epitopes in recombinant immunotoxin eliminates neutralizing and anti-drug antibodies in vivo.Cellular & molecular immunology · 2017Article
- Role of HLA-DP in the Presentation of Epitopes from the Truncated Bacterial PE38 Immunotoxin.The AAPS journal · 2017Article
- EpiSweep: Computationally Driven Reengineering of Therapeutic Proteins to Reduce Immunogenicity While Maintaining Function.Methods in molecular biology (Clifton, N.J.) · 2017Article
- OSPREY Predicts Resistance Mutations Using Positive and Negative Computational Protein Design.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Design and engineering of deimmunized biotherapeutics.Current opinion in structural biology · 2016Review
- Immunogenicity of therapeutic recombinant immunotoxins.Immunological reviews · 2016Review
- Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A.Journal of immunological methods · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Anti-drug immune responses are a unique risk factor for biotherapeutics, and undesired immunogenicity can alter pharmacokinetics, compromise drug efficacy, and in some cases even threaten patient safety. To fully capitalize on the promise of biotherapeutics, more efficient and generally applicable protein deimmunization tools are needed. Mutagenic deletion of a protein's T cell epitopes is one powerful strategy to engineer immunotolerance, but deimmunizing mutations must maintain protein structure and function. Here, EpiSweep, a structure-based protein design and deimmunization algorithm, has been used to produce a panel of seven beta-lactamase drug candidates having 27-47% reductions in predicted epitope content. Despite bearing eight mutations each, all seven engineered enzymes maintained good stability and activity. At the same time, the variants exhibited dramatically reduced interaction with human class II major histocompatibility complex proteins, key regulators of anti-drug immune responses. When compared to 8-mutation designs generated with a sequence-based deimmunization algorithm, the structure-based designs retained greater thermostability and possessed fewer high affinity epitopes, the dominant drivers of anti-biotherapeutic immune responses. These experimental results validate the first structure-based deimmunization algorithm capable of mapping optimal biotherapeutic design space. By designing optimal mutations that reduce immunogenic potential while imparting favorable intramolecular interactions, broadly distributed epitopes may be simultaneously targeted using high mutational loads.
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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.