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Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
Published on: February 6, 2018
A rapid and efficient method for generating anti-variable region monoclonal antibodies using type-1 interferons as
Kimberly Staquet1, Jamie Fisher, Roberta Lamb
1Centocor Research & Development Inc., 145 King of Prussia Rd., Radnor, PA 19087, USA. KStaquet@cntus.jnj.com
Human Antibodies
|October 27, 2006
Summary
This study introduces a new method for rapidly generating anti-drug antibodies using type 1 interferons (IFNs) and anti-CD40 antibodies. This approach accelerates the production of essential reagents for therapeutic antibody pharmacokinetic/pharmacodynamic (PK/PD) assessments.
Area of Science:
- Immunology
- Biotechnology
- Pharmacology
Background:
- Therapeutic antibody assessment requires anti-variable region monoclonal antibodies (mAbs).
- Current methods for generating these mAbs are often time-consuming.
- Developing rapid and efficient mAb generation protocols is crucial for drug development.
Purpose of the Study:
- To develop a novel, rapid immunization method for generating anti-variable region mAbs.
- To utilize type 1 interferons (IFNs) and anti-CD40 mAb as immunomodulators for enhanced B cell responses.
- To generate mAb reagents for pharmacokinetic/pharmacodynamic (PK/PD) assessments of therapeutic antibodies.
Main Methods:
- A novel immunization protocol employing type 1 interferons (IFNs) as immunomodulators.
- Co-administration of an agonistic anti-CD40 mAb to stimulate B cell proliferation.
- Generation of anti-variable region mAbs without conventional protein-denaturing adjuvants.
Main Results:
- Achieved rapid and robust generation of anti-variable region mAbs.
- Obtained comparable or increased numbers of mAbs in a significantly shorter timeframe compared to conventional methods.
- Demonstrated the efficacy of IFNs and anti-CD40 mAb in driving potent humoral immune responses.
Conclusions:
- The novel IFN-based immunostimulatory approach enables faster generation of anti-variable region mAbs.
- This non-denaturing adjuvant method may favor the presentation of conformational epitopes.
- The protocol optimizes humoral responses for rapid generation of critical reagents for therapeutic mAb evaluation.
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