Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection

Bioanalysis. 2018 Jun 1;10(11):803-814. doi: 10.4155/bio-2018-0047. Epub 2018 Apr 11.

Abstract

Aim: High drug concentrations in ocular fluids after intravitreal administration preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is therefore desirable for immunogenicity testing in ophthalmology.

Experimental: Immune complex (IC) antidrug antibody (ADA) assays were established for two species. The assays were compared with the bridging assay in ocular and plasma samples from two preclinical studies.

Results: The IC assays showed high drug tolerance, which enabled a reliable ADA detection in ocular fluids after intravitreal administration. The IC assays were superior to the bridging assay in the analysis of ocular fluids with high drug concentrations.

Conclusion: The IC assay allows a reliable ADA detection in matrices with high drug concentrations, such as ocular fluids.

Keywords: ELISA; antidrug antibody; aqueous humor; drug tolerance; immune complex assay; immunogenicity; ophthalmology; safety assessment; vitreous humor.

MeSH terms

  • Animals
  • Body Fluids / immunology*
  • Eye / immunology*
  • Humans
  • Immunoassay
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / therapeutic use*
  • Intravitreal Injections
  • Macaca fascicularis
  • Swine
  • Swine, Miniature

Substances

  • Immunoglobulin G