A kinetic enzyme immunoassay for the quantitation of antibodies to a humanized monoclonal antibody in human serum

J Pharm Biomed Anal. 1998 Apr;16(8):1317-28. doi: 10.1016/s0731-7085(97)00168-4.

Abstract

A kinetic enzyme immunoassay was developed and validated to quantitate human antibodies to the humanized monoclonal antibody CAMPATH1-1H (C1H) in human serum. The assay was configured using C1H-coated 96-well plates which were blocked with bovine serum albumin, and incubated with dilutions of human serum containing anti-C1H antibody. Antibody was detected using biotinylated C1H followed by streptavidin-conjugated alkaline phosphatase and p-nitrophenyl phosphate. Absorbance data were collected for 10 min, and mOD min-1 data were exported to MultiCalc data analysis software. A 4-parameter logistic-log algorithm was shown to model the data through the range of the standard curve within 15% of nominal values. The overall assay performance coefficient of variation by ANOVA was 9.2%. The lower limit of detection was defined at 160 Units ml-1. The anti-idiotype antibody standard stock solution is stable at 4 degrees C and at -80 degrees C for at least 11 months in buffer. The anti-idiotype antibody controls are stable for at least seven freeze-thaw cycles and at least 6 months in human serum stored at -20 degrees C. A strategy was devised by which to establish the specific antibody potency for any given batch of anti-C1H antibody standard relative to the Reference Standard. This EIA has been used to quantify and characterize anti-C1H antibody in human serum in support of clinical safety and efficacy studies.

MeSH terms

  • Alemtuzumab
  • Algorithms
  • Analysis of Variance
  • Animals
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / immunology*
  • Evaluation Studies as Topic
  • Humans
  • Immunoenzyme Techniques / methods*
  • Kinetics
  • Mice
  • Rats
  • Reference Standards

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Alemtuzumab