Open AccessImmunogenicity of antibody–drug conjugates: observations across 8 molecules in 11 clinical trials
Author(s) -
Montserrat CarrascoTriguero,
Randall C. Dere,
Marija Milojic-Blair,
Ola M. Saad,
Denise Nazzal,
Kyu Hong,
Surinder Kaur
Publication year - 2019
Publication title -
bioanalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.566
H-Index - 58
eISSN - 1757-6199
pISSN - 1757-6180
DOI - 10.4155/bio-2018-0259
Subject(s) - immunogenicity , monoclonal antibody , antibody , conjugate , drug , hapten , medicine , clinical trial , immune system , computational biology , pharmacology , immunology , biology , mathematical analysis , mathematics
Aim: To evaluate the clinical immunogenicity of eight antibody–drug conjugates (ADCs), multi-domain biotherapeutics that could theoretically pose a greater immunogenicity risk than monoclonal antibodies (mAbs) because they contain non-natural structural motifs. Methodology & results: Immunogenicity strategies and assays for these ADCs included those commonly used for conventional biotherapeutics with additional characterization. A tiered approach was adopted for testing Phase I and II clinical study samples with screening, confirmatory assays and additional domain characterization. Antidrug antibody incidences with these ADCs were within those reported for mAb biotherapeutics with no apparent impact on clinical outcomes. Conclusion: These data suggest that the ADC hapten-like structure across these eight ADCs does not appear to increase patient immune responses beyond those generally observed for mAb biotherapeutics.