A high-throughput platform for neo-antigen based cancer immunotherapy

Abstract Critical to the future progress of cancer immunotherapies is the discovery and tracking of T cells specific for cancer cells but not normal tissuesNeo antigen derived from mutations are a group of attractive antigens for cancer immunotherapyBecause they are mutated variants of self antigensthey are immunologically considered as foreign antigens and are not part of the self antigensThusthese cells are able to retain high affinity T cell receptorTCRsbearing cells that are more cytotoxic T cellsNeo antigen based therapieswhether as neo antigen vaccines or using neo antigen specific T cell receptorTCRsequences in TCR re directed adoptive cell transfer therapyhave become very promising in the fight against cancerHoweverone potential complication of neo antigen based therapies is the cross reactivity of neo antigen activated T cells might have toward the wildtype counterpart peptideWT peptideThereforehigh throughput screening for neo antigens that only induce neo antigen specific T cell responses or high throughput screening for neo antigen only TCRs is critical for the wide application of neo antigen based cancer immunotherapy approach in clinical settingsHowevercurrent technology does not permit a quick screening for none WT reactive neo antigens or none WT reactive neo antigen specific T cells from hundreds of neo antigen candidatesUsing a recently developed technology that links TCR specificities to TCR sequences at single cell level in a high throughput mannerwe aim to develop a high throughput platform for screening non cross reactive neo antigens and neo antigen specific TCRs for cancer immunotherapy Narrative Experimentally validating hundreds of neo antigens for therapeutic purpose is challengingSimilar challenge existed for identifying neo antigen specific TCRs quickly and in a high throughput mannerThe proposed technology addresses these challenges and will offer two new capabilities that will transform both cancer immunotherapy research and clinical practice