Immunogenicity Risk Assessment for Multi-specific Therapeutics
- Resource Type
- Authors
- Joleen T. White; Mark A. Kroenke; Eris Bame; Seema Kumar; Mark Milton
- Source
- The AAPS Journal
- Subject
- Pharmacology toxicology
Pharmaceutical Science
Context (language use)
Review Article
Computational biology
Risk Assessment
Antibodies
Bispecific therapeutic
Risk Factors
Antibodies, Bispecific
Humans
Medicine
Investigational New Drug Application
Multi-specific therapeutic
Tumor Necrosis Factor-alpha
Oligomeric target
business.industry
Incidence
Anti-drug antibody
Immunogenicity
Interleukin-17
Investigational New Drug
Anti-Drug Antibody
business
Risk assessment
Immunogenicity risk assessment
- Language
- ISSN
- 1550-7416
The objective of this manuscript is to provide the reader with a hypothetical case study to present an immunogenicity risk assessment for a multi-specific therapeutic as part of Investigational New Drug (IND) application. In order to provide context for the bioanalytical strategies used to support the multi-specific therapeutic presented herein, the introduction focuses on known immunogenicity risk factors. The subsequent hypothetical case study applies these principles to a specific example HC-12, based loosely on anti-TNFα and anti-IL-17A bispecific molecules previously in development, structured as an example immunogenicity risk assessment for submission to health authorities. The risk of higher incidence and safety impact of anti-drug antibodies (ADA) due to large protein complexes is explored in the context of multi-specificity and multi-valency of the therapeutic in combination with the oligomeric forms of the targets.