Optimization and qualification of a functional anti-drug antibody assay for HIV-1 bnAbs.
J Immunol Methods
; 479: 112736, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31917969
The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Testes de Neutralização
/
Anticorpos Anti-HIV
/
Infecções por HIV
/
Anticorpos Anti-Idiotípicos
/
HIV-1
/
Anticorpos Monoclonais Murinos
/
Anticorpos Amplamente Neutralizantes
Tipo de estudo:
Guideline
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article