A method for identifying a shared neoantigen-reactive T cell receptor comprising steps performed in the following specific order: (A) collecting and processing sample of a subject with a cancer; (B) obtaining a shared neoantigen by filtered the mutation sequences based on a collection of 67 off-the-shelf peptides; (C) synthesizing a long peptide corresponding to a panel of shared neoantigen and its corresponding of wild type peptides; (D) stimulating the PBMCs with the long synthetic peptides to obtain a stimulated PBMC; (E) screening the stimulated PBMC based on response of T cells is measured by interferon-γ secretion to mutant peptides and wild type peptides; (F) isolating a neoantigen-specific T cell from the screened stimulated PBMC to identify a clonotype-purified cell; (G) identifying a TCR candidate for shared neoantigen; and (H) evaluating antigenic specificity of the TCR candidate for shared neoantigen to identify a shared neoantigen-reactive TCR.
