ArticlemAbs2025
Heterogeneous and evolving epitope landscape of clinical anti-drug antibodies against multidomain biotherapeutic: a case study of TAK-186.
Article in mAbs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of anti-drug antibodies (ADAs) poses a major obstacle in the clinical development of therapeutic proteins (TPs) such as monoclonal antibodies and their derivatives. While standard multitiered ADA assays and neutralizing antibody assays offer valuable insights into the humoral immunogenicity risks of TPs, they are not sufficient to provide in-depth knowledge such as ADA epitope specificities. For complex multidomain biotherapeutics (MDBs), ADAs targeting individual domains can elicit distinct pharmacological effects. Therefore, it is crucial to implement straightforward and reliable methodologies to deconvolute ADA epitope profiles of MDBs. Herein, we report a case study using domain specificity analysis, linear peptide scanning and bioinformatic B cell epitope prediction to unveil the clinical ADA epitope landscape of TAK-186, a multidomain T cell engager that has been discontinued from clinical development. By applying this workflow, we observed strong domain specificity variability among patient samples. Furthermore, the data showed that many patients demonstrated evolved ADA epitope specificities throughout the course of the treatment. Several potential linear epitopes were identified subsequently through experimental and computational approaches. Overall, we presented in this study a practical strategy to elucidate and potentially mitigate the immunogenicity liabilities of complex biotherapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.