T cell receptors targeting tp53 hotspot mutations and uses thereof

A recombinant T cell receptor (TCR) comprising an extracellular domain that binds to a TP53 peptide, wherein the TP53 peptide comprises a R175 mutation,

• wherein the extracellular domain comprises an α chain comprising an α chain variable region and α chain constant region, and a β chain comprising a β chain variable region and a β chain constant region, wherein
• a) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 3;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 6;
• b) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 12, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 13;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 14, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 15, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 16;
• c) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 22, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 23;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 24, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 25, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 26;
• d) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 31, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 32, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 33;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 34, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 35, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 36;
• e) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 41, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 42, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 43;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 44, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 45, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 46;
• f) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 51, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 52, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 53;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 54, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 55, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 56;
• g) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 61, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 62, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 63;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 64, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 65, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 66;
• h) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 71, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 72, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 73;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 74, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 75, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 76;
• i) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 83;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 85, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 86;
• j) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 91, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 92, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 93;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 94, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 95, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 96;
• k) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 101, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 102, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 103;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 104, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 105, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 106;
• or
• l) the α chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 111, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 112, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 113;
• and the β chain variable region comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
• 114, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
• 115, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
• 116.