Epitope characterization of anti-drug antibodies—a tool for discovery and health: an overview of the necessity of early epitope characterization to avoid anti-drug antibodies and promote patient health

McMaster, Matthew; Mohr, Kelly; Page, Austin; Closmore, Adam; Towne, Francina; Brooks, Benjamin D.

doi:10.1080/14712598.2021.1863942

Cited by 6 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Different assays can have an impact on the determined immunogenicity rates and severity, as assays must be sensitive enough to detect low levels of ADA and be able to differentiate between the ADA and the therapeutic proteins including the mAbs. Two types of assays are commonly used for ADA identification: i) immunoreactivity assays that detect binding of ADAs to the therapeutics, and ii) neutralization assays for the identification of NABs [9]. Immunoreactivity assays detect the presence of any antibodies that bind to drugs in serum samples.…”

Section: Methodsmentioning

confidence: 99%

“…The two immunoreactivity assay types commonly used to screen for the detection of ADAs are ELISAs (enzyme-linked immunosorbent assays) and RIAs (radio-immunoprecipitation assays). The automated ELISAs are rapid, robust, easy to perform, while RIAs are highly sensitive, but are expensive and require radiolabels [9]. Neutralization assays, in addition to determining the presence of antibodies, the neutralizing potential of assays must also be considered.…”

Section: Methodsmentioning

confidence: 99%

“…Non-cell-based NABs assays are typically simple and do not exhibit some of the technical limitations of cell-based assays. It is important to note that there are also instances where NABs are present with no impact on drug affinity and elimination [9]. A common limitation for the neutralization assays is their low drug tolerance levels compared with typical immunoreactivity assays.…”

Section: Methodsmentioning

confidence: 99%

“…The most common three types of ELISA assays for ADA characterization include: i) sandwich ELISA, the main issue with sandwich ELISA is lack of specificity; ii) competitive immunoassay, the main issue with this method no labeled Ag; iii) bridging assay, one of the most commonly used assays [9]. Bridging assays are highly sensitive and widely accepted by both regulators and the industry for the regulatory approval of mAb therapies.…”

Section: Methodsmentioning

confidence: 99%

“…NABs prevent the therapeutic proteins from acting effectively by preventing them from binding to their pharmacological targets. However, even antibodies that do not directly affect the function of the proteins (also referred to as binding antibodies) can alter drug bioavailability and/or accelerate clearance from circulation [9]. In rare cases, immune responses can be severe, resulting in hypersensitivity reactions and even death [10].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Therapeutic Monoclonal Antibodies: Future Prospectives

2021

J Cancer Immunol

View full text Add to dashboard Cite

The development of monoclonal antibodies (mAbs) counts as one of the major medical steps forward, opening up endless possibilities for research, diagnosis, and treatment of a wide range of various diseases and disorders. Development of both humanized and fully human mAbs was expected to be non-immunogenic, that allow repeated administration without any anti-drug antibodies (ADA) responses. Unfortunately, these expectations have proven to be unrealistic. They fail to completely eliminate mAb immunogenicity and ADA formation; they have reduced the extreme immunogenicity associated with murine origin mAbs, but still, they have shown to induce antibodies that sometimes have an impact on clinical outcomes. Understanding the mechanisms of ADA generation and then factors that may influence the immunogenicity of mAbs will help us design mAbs with lower immunogenic responses. Accurate ADA detection is necessary, to provide sufficient information for patient monitoring and clinical intervention. However, ADA assays for mAb have more challenges as both the analyte and antigen (mAb) are antibodies. This short communication discusses the assessment of mAbs immunogenicity. First, we provided an overview about the development of different generations of mAbs and the immunogenicity developed upon their administration. Additionally, we also provided a conclusive review about various types of methods and their principles that have been used for assays of ADA as well as those developed for the detection of anti-trastuzumab Ab used in our study. Finally, we summarized the results and conclusions observed in our study and discussed future prospects for studying ADA developed against mAbs.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Therapeutic Monoclonal Antibodies: Future Prospectives

2021

J Cancer Immunol

View full text Add to dashboard Cite

show abstract

Whole protein or long peptides in therapeutic vaccination strategies, does it make a difference?

Mangsbo

2022

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Safety, Efficacy, and Immunogenicity of a Novel IgG Degrading Enzyme (KJ103): Results from Two Randomised, Blinded, Phase 1 Clinical Trials

Liu,

Cao,

Katial

et al. 2024

Preprint

View full text Add to dashboard Cite

The approved recombinant adeno-associated virus (AAV) intravenous drugs are limited by the high prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients’ ability to receive gene therapy and limit transfection efficacy in vivo. Based on that, we developed a novel and low immunogenicity recombinant human immunoglobulin G degrading enzyme (KJ103), which has clinical value in removing anti- AAV antibodies in vivo gene transfer. Herein, we performed two randomized, blinded, placebo-controlled, single ascending dose phase I studies in China and New Zealand, to evaluate pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy participants. The results comfirmed that KJ103 rapidly reduced IgG and maintained low levels for 1 week. The 0.01 to 0.40 mg/kg dose range of KJ103 had a favorable safety and tolerability profile in healthy participants of different ethnic and gender groups. KJ103 has low percentage of pre-existing ADAs compared to currently licensed human IgG degrading enzyme (i.e. IdeS), and the induced ADAs mostly return to baseline six months after administration. These characteristics are well suited for the treatment of immune disorders, immune rejection, and immunotherapy where pre-existing antibodies reduce efficacy (e.g. AAV-mediated gene therapy in individuals positive for pre-existing anti-AAV antibodies). The potential of KJ103 warrants further exploration.

show abstract

Epitope characterization of anti-drug antibodies—a tool for discovery and health: an overview of the necessity of early epitope characterization to avoid anti-drug antibodies and promote patient health

Cited by 6 publications

References 29 publications

Therapeutic Monoclonal Antibodies: Future Prospectives

Therapeutic Monoclonal Antibodies: Future Prospectives

Whole protein or long peptides in therapeutic vaccination strategies, does it make a difference?

Safety, Efficacy, and Immunogenicity of a Novel IgG Degrading Enzyme (KJ103): Results from Two Randomised, Blinded, Phase 1 Clinical Trials

Contact Info

Product

Resources

About