ISOLATED T CELL RECEPTORS AND METHODS OF USE THEREFOR

摘要

Provided are isolated TCRs, TCR-like molecules, and portions thereof that bind to phosphopeptide-HLA-A2 complexes. The isolated TCRs, TCR-like molecules, or portions are optionally soluble TCRs, TCR-like molecules, or portions. Also provided are isolated nucleic acids encoding the disclosed TCRs, TCR-like molecules, or portions; host cells that contain the disclosed TCRs, TCR-like molecules, or portions; pharmaceutical compositions that include the disclosed TCRs, TCR-like molecules, portions, nucleic acids, and/or T cells; kits; and methods of using the same.

主权项

1. An isolated T cell receptor (TCR), TCR-like molecule, or portion thereof that specifically binds to a phosphopeptide-HLA-A2 complex, wherein:
the phosphopeptide is RVApSPTSGV (SEQ ID NO: 2) and the isolated TCR, TCR-like molecule, or portion thereof comprises:
an alpha chain comprising a CDR3 region comprising AVSEGADRLT (amino acids 111-120 of SEQ ID NO: 4) and a beta chain comprising a CDR3 region comprising ASSLLDSSYEQY (amino acids 112-123 of SEQ ID NO: 6); oran alpha chain comprising a CDR3 region comprising AVSAGSGGKLT (amino acids 111-122 of SEQ ID NO: 8) and a beta chain comprising a CDR3 region comprising ASSDRDNYAEQF (amino acids 110-122 of SEQ ID NO: 10); or the phosphopeptide is GLLGpSPVRA (SEQ ID NO: 12) and the isolated TCR, TCR-like molecule, or portion thereof comprises an alpha chain comprising a CDR3 region comprising AVKPGGYKVV (amino acids 112-121 of SEQ ID NO: 14) and a beta chain comprising a CDR3 region comprising ASGGDTQY (amino acids 121-129 of SEQ ID NO: 16); or the phosphopeptide is RTFpSPTYGL (SEQ ID NO: 19) and the isolated TCR, TCR-like molecule, or portion thereof comprises:
an alpha chain comprising a CDR3 region comprising VLSYSNNRIF (amino acids 111-120 of SEQ ID NO: 21) and a beta chain comprising a CDR3 region comprising ASSLGGGEVF (amino acids 121-130 of SEQ ID NO: 23); oran alpha chain comprising a CDR3 region comprising VLRYGGNNKLT (amino acids 111-121 of SEQ ID NO: 25) and beta chain comprising a CDR3 region comprising ASRYRDTQY (amino acids 110-118 of SEQ ID NO: 27); or the phosphopeptide is YLDpSGIHSGV (SEQ ID NO: 29) and the isolated TCR, TCR-like molecule, or portion thereof comprises an alpha chain comprising a CDR3 region comprising AIPPGTGSKLS (amino acids 108-118 of SEQ ID NO: 32) and a beta chain comprising a CDR3 region comprising ASSQGQKGY (amino acids 110-118 of SEQ ID NO: 34); or the phosphopeptide is YLDpSGIHSGA (SEQ ID NO: 30) and the isolated TCR, TCR-like molecule, or portion thereof comprises an alpha chain comprising a CDR3 region comprising ATGPNTNKVV (amino acids 110-119 of SEQ ID NO: 36) and a beta chain comprising a CDR3 region comprising ASSQGGAEQF (amino acids 110-119 of SEQ ID NO: 38).