A rapid and efficient method for generating anti-variable region monoclonal antibodies using type-1 interferons as immune modulators - Monoclonal Antibodies

A rapid and efficient method for generating anti-variable region monoclonal antibodies using type-1 interferons as immune modulators
2006
Staquet K, Fisher J, Lamb R, Bannish G, Duchala C, Mbow ML, Rycyzyn MA, Giles-Komar J.
Centocor Research & Development Inc., 145 King of Prussia Rd., Radnor, PA 19087, USA
Hum Antibodies.
The generation of anti-variable region monoclonal antibodies (mAbs) against therapeutic antibodies is essential in the pharmacokinetic/pharmacodynamic (PK/PD) assessments of the drugs in clinical study samples. Sandwich EIA and other methods are typically employed to achieve sensitivity and selectivity for the PK/PD analyses. These assays usually require generation of mAb reagents that bind specifically to the drug in non-competing pair combinations. Thus, large panels of anti-variable region mAbs must be generated in an expeditious manner to increase the probability of success. Herein we describe a novel immunization method that utilizes type 1 interferons (IFNs) as immunomodulators coupled with an agonistic anti-CD40 mAb as a B cell proliferative agent to drive immune responses. This novel protocol allows for rapid and robust mAb reagent generation without the use of conventional protein-denaturing adjuvants. The use of IFNs allowed for the generation of comparable and in some cases, increased numbers of anti-variable region mAbs in a dramatically shorter timeframe. This IFN based, immunostimulatory approach utilizing a non-denaturing adjuvant, likely presents conformational epitopes and may optimize the humoral response for the rapid generation of anti-variable region reagents to therapeutic mAb candidates.
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