Abstract: This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize a particular HER2 mutation, such as TCRs that recognize the Y772dupYVMA mutation in HER2 presented on HLA-A*02:01. Accordingly, aspects of the disclosure relate to an engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs with respect to this antigen. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.

Abstract: This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize EGFR neoantigens comprising L858R mutations and restricted to HLA class I A11 allotype. Accordingly, aspects of the disclosure relate to a polypeptide comprising an antigen binding variable region comprising the amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure.

Abstract: Provided are compositions including EGFR mutant peptides that bind to HLA class I and/or HLA class II complexes and compositions comprising a plurality of such peptides. Methods for treating EGFR-mutant cancers with peptides of the embodiments are likewise provided. Methods for expanding related populations of immune effector cells, such as T cells, are also provided.