High throughput approach for generating human monoclonal antibodies

DESCRIPTION provided by applicant Thanks to their exquisite specificity and sensitivity monoclonal antibodies Mab have found a broad application in research diagnosis and therapy For treatment of human diseases fully human antibodies are the most desirable as they are generally not immunogenic and well tolerated While there are several existing approaches for generation of antibodies the processes are still time consuming labor intensive and unpredictable of success To simplify and to accelerate the generation of fully human antibodies a novel non animal approach for antibody production is proposed The objective will be achieved by using a Self Diversifying Human Antibody Library SHALib effectively displayed on yeast cell surface SHALib will provide a diverse array of antibodies in vitro without the need of animal immunization and potential necessary humanization of the antibody Starting from a naive antibody library from healthy human donors antibodies with high affinity and specificity to various targets will be generated and selected through repeated rounds of systematic evolution by somatic hypermutation target specific enrichment and fluorescence activated cell sorting Since this is a non animal system the platform can generate human antibodies against toxins pathogens self antigens and the like which are by nature difficult to obtain As a proof of principle in phase I we will develop human antibodies to five selected targets of therapeutic importance The targets are for the treatment of high cholesterol PCSK rheumatoid arthritis MMP and MMP and cancer MMP and regulatory T cell protein CD In Phase II the platform will be used to develop human monoclonal antibodies to at least targets that are involved in different human diseases The platform will allow generating quickly human monoclonal antibodies that are of therapeutic potential PUBLIC HEALTH RELEVANCE As result of this project an innovative approach for rapid generation of human monoclonal antibodies will be developed and valuable antibody reagents for treatment of human diseases will be generated The platform will have a broad application in accelerating generation of human antibodies of therapeutic significance