ReviewmAbs
Have we overestimated the benefit of human(ized) antibodies?
Review in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Antibody-recruiting molecules: an emerging paradigm for engaging immune function in treating human disease.ACS chemical biology · 2012Pooled it
- The pharmacokinetics and pharmacodynamics of TOL101, a murine IgM anti-human αβ T cell receptor antibody, in renal transplant patients.Clinical pharmacokinetics · 2014Trial
- First-in-human study of the safety and efficacy of TOL101 induction to prevent kidney transplant rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Trial
- Stratification of antibody-positive subjects by antibody level reveals an impact of immunogenicity on pharmacokinetics.The AAPS journal · 2013Trial
- Humoral response to catumaxomab correlates with clinical outcome: results of the pivotal phase II/III study in patients with malignant ascites.International journal of cancer · 2012Trial
- Antibody Humanization.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy.Antimicrobial agents and chemotherapy · 2024Article
- Construction of Human Immune and Naive scFv Phage Display Libraries.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Radioimmunotherapy for solid tumors: spotlight on Glypican-1 as a radioimmunotherapy target.Therapeutic advances in medical oncology · 2021Article
- Sagacity in antibody humanization for therapeutics, diagnostics and research purposes: considerations of antibody elements and their roles.Antibody therapeutics · 2020Review
- Clinical Immunogenicity Risk Assessment Strategy for a Low Risk Monoclonal Antibody.The AAPS journal · 2020Review
- Recombinant Antibodies against Mycolactone.Toxins · 2019Article
- Preclinical optimization of antibody-based radiopharmaceuticals for cancer imaging and radionuclide therapy-Model, vector, and radionuclide selection.Journal of labelled compounds & radiopharmaceuticals · 2018Review
- AnticalinBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018Review
- IgG Antibody 3D Structures and Dynamics.Antibodies (Basel, Switzerland) · 2018Review
- Article
- Secukinumab Demonstrates Significantly Lower Immunogenicity Potential Compared to Ixekizumab.Dermatology and therapy · 2018Article
- Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy.EBioMedicine · 2017Article
- Clinical Pharmacokinetics and Pharmacodynamics of Biologic Therapeutics for Treatment of Systemic Lupus Erythematosus.Clinical pharmacokinetics · 2017Review
- CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.
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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.