Monoclonal antibody humanness score and its applications

Area of Science:

• Immunology
• Biotechnology
• Drug Development

Background:

• Monoclonal antibody therapeutics are increasingly used for diverse diseases like cancer and autoimmune disorders.
• Antibody therapeutics vary in human sequence content, impacting clinical immunogenicity.
• More human-like antibodies generally exhibit reduced immunogenicity in trials.

Purpose of the Study:

• To develop and validate a method for quantifying the humanness of monoclonal antibody variable regions.
• To analyze the correlation between antibody humanness and immunogenicity.
• To compare the immunogenicity of fully human and humanized antibodies.

Main Methods:

• Created and analyzed a database of human antibody sequences.
• Developed a method to calculate a 'humanness score' for antibody variable regions.
• Compared humanness scores and immunogenicity data for therapeutic antibodies.

Main Results:

• The developed method accurately distinguishes human from non-human antibodies.
• Increased antibody humanness score is significantly correlated with decreased immunogenicity.
• Fully human and highly humanized antibodies showed similar immunogenicity profiles.

Conclusions:

• Humanizing antibodies and confirming their humanness can effectively mitigate immunogenicity, similar to fully human antibodies.
• A public website was launched to calculate antibody humanness scores.
• This humanness scoring tool aids preclinical development of monoclonal antibody therapeutics.