ArticleFrontiers in immunology2020
The Irony of Humanization: Alemtuzumab, the First, But One of the Most Immunogenic, Humanized Monoclonal Antibodies.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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
19 citing papers in PubMed.
- Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab.Frontiers in immunology · 2021Trial
- Long-term effectiveness and cost-effectiveness of testing for alemtuzumab antidrug antibodies to guide treatment in multiple sclerosis: a modelling study.The European journal of health economics : HEPAC : health economics in prevention and care · 2026Article
- Impacts of anti-drug antibodies on pharmacokinetic and pharmacodynamic actions of cell-permeable middle molecule peptide drug.The Journal of pharmacology and experimental therapeutics · 2025Article
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.Cell reports. Medicine · 2024Article
- Unlocking the potential of iPSC-derived immune cells: engineering iNK and iT cells for cutting-edge immunotherapy.Frontiers in immunology · 2024Review
- Article
- Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence.Journal of clinical medicine · 2023Article
- Review
- Next-generation antibody-based therapies in neurology.Brain : a journal of neurology · 2022Review
- Immunogenicity of Monoclonal Antibodies and the Potential Use of HLA Haplotypes to Predict Vulnerable Patients.Frontiers in immunology · 2022Review
- Impact of histone modifier-induced protection against autoimmune encephalomyelitis on multiple sclerosis treatment.Frontiers in neurology · 2022Review
- Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis.Neurology · 2021Article
- Rituximab induced cytokine release syndrome in an MS patient: A case report.Clinical case reports · 2021Article
- Targeting Strategies for Enhancing Paclitaxel Specificity in Chemotherapy.Frontiers in cell and developmental biology · 2021Review
- Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center.Frontiers in neurology · 2021Article
- The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.Multiple sclerosis and related disorders · 2020Review
- Detecting and predicting neutralization of alemtuzumab responses in MS.Neurology(R) neuroimmunology & neuroinflammation · 2020Article
- Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alemtuzumab was designed to reduce the immunogenicity of the parent CD52-specific rat immunoglobulin. Although originally marketed for use in cancer (Mabcampath®), alemtuzumab is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada®). Perhaps due to its history as the first humanized antibody, the potential of immunogenicity of the molecule has been considered inconsequential, and anti-drug antibodies (ADA) responses were similarly reported as being clinically insignificant. Nonetheless, despite humanization and depletion of peripheral T and B cells, alemtuzumab probably generates the highest frequency of binding and neutralizing ADA of all humanized antibodies currently in clinical use, and they occur rapidly in a large majority of people with MS (pwMS) on alemtuzumab treatment. These ADA appear to be an inherent issue of the biology of the molecule-and more importantly, the target-such that avoidance of immunogenicity-related effects has been facilitated by the dosing schedule used in clinical practice. At the population level this enables the drug to work in most pwMS, but in some individuals, as we show here, antibody neutralization appears to be sufficiently severe to reduce efficacy and allow disease breakthrough. It is therefore imperative that efficacy of lymphocyte depletion and the anti-drug response is monitored in people requiring additional cycles of treatment, notably following disease breakthrough. This may help inform whether to re-treat or to switch to another disease-modifying treatment.
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