Antibody Humanization Service - Creative Biolabs (Updated Version)

Summary

Creative Biolabs offers cutting-edge de novo antibody humanization technology and services to enhance monoclonal antibody efficacy. This process addresses the limitations of mouse-derived antibodies, which can cause immunogenic reactions in humans. By utilizing methods like CDR grafting, resurfacing, and change shuffling, Creative Biolabs creates fully humanized antibodies with optimized affinity and specificity. Their platform supports humanization of antibodies from various species, including unique expertise in monkey antibody humanization. With advanced antibody sequencing techniques, the company aims to revolutionize therapeutic and diagnostic antibody development for global clients.

Takeaways

• 😀 Antibody humanization is the process of modifying monoclonal antibodies to reduce immunogenicity and improve their effectiveness in human treatments.
• 😀 Monoclonal antibodies are important in disease prevention, diagnosis, and treatment, but mouse-derived antibodies can cause immune responses in humans.
• 😀 The most widely used humanization method is CDR grafting, which replaces the complementary determining regions (CDRs) of mouse antibodies with those from human antibodies.
• 😀 Humanization strategies can also involve reshaping the surface residues of antibodies using a method called resurfacing, to avoid creating new antigenic epitopes.
• 😀 The humanization process often involves iterative design, including sequence analysis, 3D modeling, and functional testing of the modified antibody.
• 😀 The 'change shuffling' method utilizes phage display technology to create fully humanized antibodies, overcoming human anti-mouse antibody responses.
• 😀 Change shuffling can result in antibodies with higher affinities than the original mouse antibody and produce multiple versions for therapeutic flexibility.
• 😀 Creative Biolabs has extensive experience in humanizing antibodies from various species, including mouse, rat, rabbit, llama, and even monkey antibodies.
• 😀 The company offers specialized services for humanizing bovine ultra-long single-chain antibodies, which are effective against challenging antigen families.
• 😀 Creative Biolabs has developed a GH8 platform for optimizing human antibodies with minimal immunogenicity while retaining parental affinity and specificity.
• 😀 The company also offers de novo antibody sequencing services, using advanced technologies such as database-assisted shotgun sequencing to derive antibody amino acid sequences.

Q & A

What is antibody humanization and why is it important?

Antibody humanization refers to the process of modifying non-human antibodies, particularly mouse monoclonal antibodies, to make them more similar to human antibodies. This is important because humanized antibodies are less likely to cause immune responses in humans, enhancing their effectiveness and safety in treating diseases.

Why are mouse-derived monoclonal antibodies not ideal for human use?

Mouse-derived monoclonal antibodies are often immunogenic, meaning they can trigger immune responses in humans, which can reduce their effectiveness. Additionally, they may not effectively activate human complement and FC receptor systems, which limits their therapeutic application.

What are the common methods for humanizing antibodies?

The most common methods for humanizing antibodies include CDR grafting, SDR transfer, and resurfacing. These methods aim to replace parts of the mouse antibody with human sequences to reduce immunogenicity while retaining the antibody's specificity and affinity.

What is CDR grafting?

CDR grafting is a technique where the complementarity-determining regions (CDRs) of a mouse monoclonal antibody are inserted into the corresponding regions of a human antibody, either partially or fully, to produce a humanized antibody with similar antigen-binding properties.

What is the challenge with CDR grafting and how can it be addressed?

CDR grafting may introduce new antigenic epitopes, which could lead to immune responses. This challenge can be addressed by using methods like resurfacing, which replaces the surface residues of the antibody with human counterparts to reduce the risk of immune reactions.

What is the third-generation antibody humanization method mentioned in the transcript?

The third-generation antibody humanization method, known as 'change shuffling,' involves replacing mouse antibody fragments with human antibody fragments using phage display technology. This method results in fully humanized antibodies, overcoming the human anti-mouse antibody response and improving affinity.

How does change shuffling work in antibody humanization?

In change shuffling, the light chain of a rodent antibody is replaced with a light chain from a human antibody library. After screening, the heavy chain is also replaced with a human antibody library fragment, creating a fully humanized antibody. This process mimics natural antibody selection and evolution.

What unique service does Creative Biolabs offer in the field of antibody humanization?

Creative Biolabs offers a wide range of antibody humanization services, including the humanization of monoclonal antibodies derived from various species such as canine, bovine, rabbit, llama, and even monkey antibodies. They also provide specialized services like the humanization of bovine ultra-long CDR3 antibodies.

What is the GH8 platform mentioned by Creative Biolabs?

The GH8 platform is an innovative technology developed by Creative Biolabs to produce humanized antibodies with excellent human-like properties. This platform generates antibodies with minimal immunogenicity while retaining the original antibody’s affinity and specificity.

What is the role of de novo antibody sequencing in antibody humanization?

De novo antibody sequencing helps in deriving the amino acid sequences of antibodies by analyzing tandem mass spectra. This technology aids in the precise identification of antibody structures and is critical for creating humanized antibodies with accurate sequence optimization.