Background: Monoclonal antibody therapeutics are rapidly gaining in popularity for the treatment of a myriad of\r\ndiseases, ranging from cancer to autoimmune diseases and neurological diseases. Multiple forms of antibody\r\ntherapeutics are in use today that differ in the amount of human sequence present in both the constant and\r\nvariable regions, where antibodies that are more human-like usually have reduced immunogenicity in clinical trials.\r\nResults: Here we present a method to quantify the humanness of the variable region of monoclonal antibodies\r\nand show that this method is able to clearly distinguish human and non-human antibodies with excellent\r\nspecificity. After creating and analyzing a database of human antibody sequences, we conducted an in-depth\r\nanalysis of the humanness of therapeutic antibodies, and found that increased humanness score is correlated with\r\ndecreased immunogenicity of antibodies. We further discovered a surprisingly similarity in the immunogenicity of\r\nfully human antibodies and humanized antibodies that are more human-like based on their humanness score.\r\nConclusions: Our results reveal that in most cases humanizing an antibody and confirming the humanness of the\r\nfinal form may be sufficient to eliminate immunogenicity issues to the same extent as using fully human\r\nantibodies. We created a public website to calculate the humanness score of any input antibody sequence based\r\non our human antibody database. This tool will be of great value during the preclinical drug development process\r\nfor new monoclonal antibody therapeutics
Loading....