March 23, 2021

Yuning Wang, PhD*,1, Jennifer Crha, MSc#,1, Jessica Barber, MPH#,1
*Author
#Reviewer
1Rapid Novor, Inc.

Abstract

Mouse monoclonal antibodies (mAbs) are highly attractive for manipulation for therapeutic applications as their manufacturing is relatively easy and well-established compared to mAbs derived from larger animal models. However, they also pose several challenges which limits their use as therapeutic agents. Particularly, their short serum half-life, inability to trigger human effector functions, and their immunogenicity  that leads to recognition by the patients’ immune system (i.e., human anti-mouse antibody response). Through protein engineering, murine antibodies have been transformed into structures more similar to human antibodies without sacrificing their binding specificity or affinity, while reducing immunogenicity. In this review, current antibody engineering technologies are explored while discussing how de novo protein sequencing can enhance engineering and characterization efforts for robust mAb therapeutic development.

Key Takeaways

  • Thanks to antibody engineering, it has been possible to manipulate antibody structure to generate more robust antibodies while lowering immunogenicity
  • However, current methods of generating monoclonal antibodies, and techniques in antibody engineering tend to heavily rely on DNA sequencing methodologies
  • Though critical in antibody engineering, DNA manipulation techniques are simply blind to data that protein sequencing can provide
  • Thanks to protein sequencing, engineered antibodies can be further characterized for more potent and safely engineered mAb drugs

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Content

  1. Antibody Humanization has Strengthened our Therapeutic Ability
  2. Antibody Fragments and Engineered Variants Open Paths to Many Applications
  3. Techniques to Generate and Engineer Therapeutic Antibodies
  4. Applications of De Novo Protein Sequencing in Antibody Engineering
  5. Case Study: Next Generation Targeted Cytokine Therapies with De Novo Antibody Sequencing
  6. Conclusions
  7. References

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We Have Sequenced 3000+ Antibodies and We Are Eager to Help You.

Through next generation protein sequencing, Rapid Novor enables reliable discovery and development of novel reagents, diagnostics, and therapeutics. Thanks to our Next Generation Protein Sequencing and antibody discovery services, researchers have furthered thousands of projects, patented antibody therapeutics, and developed the first recombinant polyclonal antibody diagnostics.

Talk to Our Scientists.

We Have Sequenced 3000+ Antibodies and We Are Eager to Help You.

Through next generation protein sequencing, Rapid Novor enables timely and reliable discovery and development of novel reagents, diagnostics, and therapeutics. Thanks to our Next Generation Protein Sequencing and antibody discovery services, researchers have furthered thousands of projects, patented antibody therapeutics, and ran the first recombinant polyclonal antibody diagnostics

Talk to our scientists. We have sequenced over 3000 antibodies and we are eager to help you.