Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity.

Area of Science:

• Immunology
• Biotechnology
• Pharmacology

Background:

• Anti-drug antibodies (ADAs) pose a significant clinical challenge in biotherapeutic treatments.
• The immune response involves CD4+ T cells, memory B cells, and long-lived plasma cells.

Purpose of the Study:

• To review methods for predicting and identifying T-cell and B-cell epitopes in therapeutic proteins.
• To discuss approaches for characterizing ADA responses in humans.
• To explore strategies for reducing or reversing immunogenicity.

Main Methods:

• Epitope prediction and experimental identification for T cells and B cells.
• Phenotyping ADA responses using T-cell stimulation assays.
• Assessing ADA titers, epitopes, and isotypes using established and novel techniques.

Main Results:

• Factor VIII immunogenicity is a key area of research.
• Various methods exist to characterize ADA development and characteristics.
• Rational protein engineering can mitigate immunogenicity.

Conclusions:

• Understanding and managing ADA development is crucial for biotherapeutic efficacy.
• Novel tolerance-inducing strategies are vital for future treatments.
• Combined approaches of protein engineering and tolerance induction will be key.