Therapeutic antibodies have shown great success for treatment of cancer and other human diseases. Most antibody therapies currently in clinical use are conventional monoclonal antibodies. Because antibody therapeutics provides good safety profiles and target specificity, there is a trend toward development of advanced antibody drug modalities. These include antibodies linked to small molecule drugs (ADCs), bispecific antibodies and antibody fused to proteins, and antibody fragments (scFv) linked to T cell receptor complexes for use in CAR-T cell therapy. This core will provide innovative antibody engineering technologies for three key advanced antibody based drug modalities. One of the modal...

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Therapeutic antibodies have shown great success for treatment of cancer and other human diseases. Most antibody therapies currently in clinical use are conventional monoclonal antibodies. Because antibody therapeutics provides good safety profiles and target specificity, there is a trend toward development of advanced antibody drug modalities. These include antibodies linked to small molecule drugs (ADCs), bispecific antibodies and antibody fused to proteins, and antibody fragments (scFv) linked to T cell receptor complexes for use in CAR-T cell therapy. This core will provide innovative antibody engineering technologies for three key advanced antibody based drug modalities. One of the modalities is antibody-drug conjugates (ADCs) that combine antibody tumor specificity with the potent killing function of cytotoxic small molecules in one drug through stable chemical linkers. The ADC modality has great potential to limit the toxicity of conventional chemotherapy. A second modality is bispecifc antibodies (BsAbs) that target two cancer antigens or two epitopes on the same cancer antigen, incorporating the specificities and properties of two distinct monoclonal antibodies (mAbs) into a single molecule. BsAbs can elicit synergistic activities and provide better therapeutic efficacy. The third modality is construction of scFv antibody fragments tailored for chimeric antigen receptor-modified T cells (CAR-T) constructs. CAR-T is emerging as an important T cell-based cancer therapy. The antigen specific antibody fragment (scFv) is a key CAR-T component. We constructed a high diversity phage-displayed human antibody library of scFv fragments. These fragments can be used directly for CAR constructs. By engineering from conventional monoclonal antibodies to these advanced drug modalities, the proposed Core will strength translational capability of the academic research community in the state of Texas and promote the development of life-saving cancer immunotherapies.

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