A streamlined, high-throughput platform for validation of cancer antigen presentation and isolation of cancer antigen reactive T cells

点击翻译按钮获取中文摘要

Abstract T cell receptor (TCR) based cancer immunotherapies, either infusing expanded patient autologous tumor- specific T cells or infusing cancer-specific TCR engineered autologous T cells, have shown great clinical benefit in several types of cancer. However, two challenges have prevented the broad application of these therapies to many types of cancer. First, there lacks a quick and sensitive method to detect patient-specific presentation of cancer antigen peptides on the surface of tumor cells. Second, there lacks a rapid method for the isolation of antigen-specific T cells that can be propagated quickly in vitro to meet the real-time needs of adoptive cell transfer therapy. These challenges have become road blocks for the application of TCR based cancer immunotherapy to many types of cancer and have prevented the exploration of other classes of cancer-antigens in addition to neo-antigens (NeoAs) that also have therapeutic potential, such as cancer germline antigens (CGA). In this study, we propose the development of AbTR (Antigen sensing-based T cell Recall) technology to address these two critical challenges in large scale. The AbTR technology will provide a quick and streamlined path to identify cancer antigens presented on tumor cell from hundreds of possible targets and isolate many antigen- specific T cell clones that are functionally capable of killing tumor cells and are ready to be used in adoptive cell transfer therapy. The success of the project address two urgent needs in cancer immunotherapy. This technology not only can be applied to all types of cancer but may also be relevant for the study of other immunological diseases, such as infection and autoimmune diseases.