Pre-existing Antibody: Biotherapeutic Modality-Based Review

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Pre-existing antibodies (immunoglobulins) against biotherapeutics are detected in drug-naïve individuals.
• These antibodies can be specific or cross-reactive to epitopes on biotherapeutic compounds.
• Environmental exposures to similar proteins or glycans are potential causes.

Purpose of the Study:

• To review the relationships between biotherapeutic modalities and pre-existing antibodies.
• To understand the nature, prevalence, and clinical consequences of these antibodies.
• To discuss factors that may interfere with anti-drug antibody (ADA) assays.

Main Methods:

• Literature review of pre-existing antibodies in biotherapeutic drug development.
• Analysis of the impact of pre-existing antibodies on drug immunogenicity.
• Discussion of interfering factors in ADA assay development.

Main Results:

• Pre-existing antibodies are an immunogenicity risk factor requiring careful evaluation.
• Clinical consequences vary widely, depending on the drug and indication.
• Evidence for pre-existing antibodies often emerges during ADA assay development.

Conclusions:

• Pre-existing antibodies represent a critical consideration in biotherapeutic development.
• Understanding their origins and impact is crucial for patient safety and therapeutic success.
• Awareness of assay interferences is essential for accurate immunogenicity assessment.