Chimeric antigen receptors to HER2 and methods of use thereof

A nucleic acid encoding a chimeric antigen receptor (CAR) for binding HER2, said CAR comprising:

• a) an antigen-specific targeting region (ASTR) that binds to HER2 protein;
• b) a transmembrane domain;
• and
• c) an intracellular activating domain, wherein the transmembrane domain is located between the ASTR and the intracellular activating domain, and wherein the ASTR comprises a heavy chain variable region comprising three complementarity determining regions (CDRs), said CDRs having sequences HCDR1, HCDR2, and HCDR3, wherein:
• (SEQ ID NO:
• 131)
• the HCDR1 sequence is GFNIKDTYIH;
• (SEQ ID NO:
• 137)
• the HCDR2 sequence is X1IYPTNGYTX2YADSVKG;
• and
• (SEQ ID NO:
• 133)
• the HCDR3 sequence is WGGDGFYAMDY;
• and the ASTR comprises a light chain variable region including three CDRs having sequences LCDR1, LCDR2, and LCDR3, wherein:
• (SEQ ID NO:
• 142)
• the LCDR1 sequence is RASQDVNTX3VA;
• (SEQ ID NO:
• 135)
• the LCDR2 sequence is SASFLYS;
• and
• (SEQ ID NO:
• 143)
• the LCDR3 sequence is QQX4YTTPPT,
• wherein the combination of X1, X2, X3, and X4 is, respectively:
• K, R, A, and H;
• K, E, A, and H;
• R, R, D, and H;
• K, E, D, and H;
• R, R, A, and D;
• R, R, D, and D;
• K, R, D, and D;
• K, E, D, and D;
• R, R, A, and E;
• K, E, A, and E;
• K, R, D, and E;
• or K, E, D, and E.