MAbstract® technology: from antibody discovery to medical innovation

Crucell’s proprietary MAbstract® technology can be used to rapidly select target-binding antibodies of interest and to identify unique targets on proteins, viruses, bacteria and live cells or tissues. The technology is also useful for identifying the specific binding regions for antibodies on antigens (molecules recognized by the immune system). These binding regions (epitopes) on antigens can be used for the design of vaccines or small-molecule inhibitors.

 

 

Competitive edge

Traditional technologies for generating and selecting monoclonal antibodies (mAbs) have the drawback of generating limited repertoires and using inefficient selection procedures. Crucell’s scientists have found that the combination of phage-display, MAbstract® technology and optimized reformatting procedures results in fast recovery of monoclonal antibodies with the desired properties. Why put link for phage here (whereas it has been mentioned  and explained already several times before and again in next section.

 

 

How it works

Crucell uses so-called phage-display technology for antibody discovery. A bacteriophage, or phage, is a virus that can infect and multiply in bacteria. Phages can be genetically engineered to contain a DNA sequence encoding  the antigen-binding part of a human antibody that is expressed on the phage surface. Many genetic antibody sequences are expressed in a bacteriophage library in the form of fusions with the bacteriophage coat protein, so that they are displayed on the surface of the phage particles. The antibody parts displayed correspond to the genetic sequence within the phage. To identify and subsequently isolate relevant antibodies, the phage library is exposed to the target, which may be an entire pathogen or an isolated antigen. Phages displaying antibodies that interact with the target molecules are harvested. The DNA within the interacting phage contains the sequences of interacting antibody, and following further bacterial-based amplification, can be sequenced to identify the relevant antibody fragment. By genetic engineering this antibody sequence can be reformatted in a fully human monoclonal antibody with the desired specificity and function. Potent antibodies have been rapidly isolated from universally applicable, ready-made libraries of a very large size.

 

 

Availability

Crucell has generated several very large antibody phage display libraries built from normal donors and also from subsets of specialized B-cells. These libraries can be used immediately for selection of antibodies against any given antigen. Furthermore, Crucell can build new libraries from immunized or infected donors, producing the desired antibody specificities in less than 8 weeks. Crucell has developed the in-house expertise to evaluate antibodies in functional assays in a high-throughput manner. A typical antibody discovery program can thus be run in less than 9 months starting from the construction of the libraries to the delivery of a lead antibody clone.

Experience

Crucell’s antibody discovery group is internationally recognized for the rapid discovery of potent monoclonal antibodies against a range of infectious diseases.

 

For example:

• Crucell was the first group worldwide to generate fully human mAbs that effectively controlled SARS coronavirus infection in a relevant animal model and the first to discover human mAbs against West Nile virus.  
• The World Health Organization (WHO) has endorsed Crucell’s rabies mAb combination, which has already produced very promising results in phase 1 and 2 clinical trials.
• In December 2008, Crucell scientists reported the discovery of a new class of human mAbs neutralizing a broad range of influenza virus subtypes. A flu-mAb product based on this breakthrough discovery has entered preclinical development, with the support of Crucell’s strategic partner Johnson & Johnson.
• In August 2009, Crucell obtained an exclusive license from Stanford University (Palo Alto, California) for the development of an antibody combination against hepatitis C virus (HCV). Crucell is evaluating a large panel of fully human mAbs against HCV in a proof of concept phase and has reported promising results.