ArticleProceedings of the National Academy of Sciences of the United States of America2014
Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 3 of them syntheses 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
248 citing papers in PubMed, 3 syntheses or guidelines pooled it, 441 citations in OpenAlex.
- Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review.Frontiers in immunology · 2024Pooled it
- Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021Pooled it
- Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS).The British journal of dermatology · 2020Pooled it
- Pharmacokinetics, Immunogenicity, and Safety of a Modified YTE Antibody in Healthy Adults.Clinical pharmacology in drug development · 2026Trial
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- Trial
- Dupilumab in Patients With Chronic Spontaneous Urticaria: Phase 3 LIBERTY-CSU CUPID Randomized Clinical Trials.JAMA dermatology · 2026Trial
- Dupilumab Treatment Up to 5 Years Shows No Clinically Meaningful Changes in Laboratory Parameters in Adults with Moderate-to-Severe Atopic Dermatitis.Advances in therapy · 2026Trial
- Dupilumab Efficacy in Children With Eosinophilic Esophagitis With Prior Swallowed Topical Corticosteroid Use: A Subgroup Analysis.The American journal of gastroenterology · 2026Trial
- Peak Nasal Inspiratory Flow and the Association with Nasal Obstruction in Patients with Severe CRSwNP from the SINUS-24/-52 Studies.Advances in therapy · 2025Trial
- Dupilumab efficacy by disease severity in pediatric type 2 asthma.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025Trial
- Dupilumab Efficacy and Safety in Patients With Persistent Asthma: Asia-Pacific Region.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025Trial
- Dupilumab Plus Medium-Dose Inhaled Corticosteroid (ICS) Improves Outcomes Compared With Placebo Plus Continued High-Dose ICS in Children With Uncontrolled Moderate-to-Severe Type 2 Asthma.Pediatric pulmonology · 2025Trial
- A TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans.JCI insight · 2025Trial
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- GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial.Nature communications · 2025Trial
- Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients With Peanut Allergy.Allergy · 2025Trial
- Association Between Smell Loss, Disease Burden, and Dupilumab Efficacy in Chronic Rhinosinusitis with Nasal Polyps.American journal of rhinology & allergy · 2025Trial
- Dupilumab is Efficacious in Young Children with Atopic Dermatitis Regardless of Type 2 Comorbidities.Advances in therapy · 2024Trial
- Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.Cancer medicine · 2024Trial
188 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.
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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.