Magea1 immunogenic peptides, binding proteins recognizing magea1 immunogenic peptides, and uses thereof
AssigneeTScan Therapeutics, Inc.
InventorsNancy Nabilsi, Yifan Wang, Jenny Tadros, Mollie M. Jurewicz, Gavin MacBeath
Life of this patent
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Abstract
Provided herein are MAGEA1 immunogenic peptides, binding proteins recognizing MAGEA1 immunogenic peptides, and uses thereof.
Claims30
-55. (canceled)
A binding protein that binds a polypeptide comprising an immunogenic peptide comprising or consisting of a peptide epitope selected from VLEYVIKV (SEQ ID NO:
- 2), KVLEYVIK (SEQ ID NO:
- 3), and peptide sequences listed in Table 1, optionally wherein the binding protein:
- 1) is an antibody, an antigen-binding fragment of an antibody, a TCR, an antigen-binding fragment of a TCR, a single chain TCR (scTCR), a chimeric antigen receptor (CAR), or a fusion protein comprising a TCR and an effector domain;
- 2) comprises:
- a) a TCR alpha chain variable (Vα) domain comprising CDR1 having at least about 80% identity to residues 48-53 of SEQ ID NO:
- 9 (VSGLRG), CDR2 having at least about 80% identity to residues 71-77 of SEQ ID NO:
- 9 (LYSAGEE), and CDR3 having at least about 80% identity to residues 109-119 of SEQ ID NO:
- 9 (CAVSYGONFVF);
- and
- b) a TCR beta chain variable (Vβ) domain comprising CDR1 having at least about 80% identity to residues 46-50 of SEQ ID NO:
- 11 (SGHTS), CDR2 having at least about 80% identity to residues 68-73 of SEQ ID NO:
- 11 (YDEGEE), and CDR3 having at least about 80% identity to residues 110-123 of SEQ ID NO:
- 11 (CASSLGQLNTEAFF);
- 3) comprises:
- a) a TCR alpha chain variable (Vα) domain with at least about 80% identity to residues 1-130 of SEQ ID NO:
- 9;
- and
- b) a TCR beta chain variable (Vβ) domain with at least about 80% identity to residues 1-133 of SEQ ID NO:
- 11;
- 4) comprises:
- a) a TCR alpha chain with at least about 80% identity to the sequence of SEQ ID NO:
- 9;
- and
- b) a TCR beta chain with at least about 80% identity to the sequence of SEQ ID NO:
- 11;
- 5) comprises:
- a) a T cell receptor (TCR) alpha chain CDR sequence with at least about 80% identity to a TCR alpha chain CDR sequence selected from the group consisting of TCR alpha chain CDR sequences listed in Table 2;
- and/or
- b) a TCR beta chain CDR sequence with at least about 80% identity to a TCR beta chain CDR sequence selected from the group consisting of TCR beta chain CDR sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M;
- 6) comprises:
- a) a TCR alpha chain variable (Vα) domain sequence with at least about 80% identity to a TCR Vα domain sequence selected from the group consisting of TCR Vα domain sequences listed in Table 2;
- and/or
- b) a TCR beta chain variable (Vβ) domain sequence with at least about 80% identity to a TCR Vβ domain sequence selected from the group consisting of TCR Vβ domain sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M;
- 7) comprises:
- a) a TCR alpha chain sequence with at least about 80% identity to a TCR alpha chain sequence selected from the group consisting of TCR alpha chain sequences listed in Table 2;
- and/or
- b) a TCR beta chain sequence with at least about 80% identity to a TCR beta chain sequence selected from the group consisting of TCR beta chain sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M;
- 8) comprises:
- a) a TCR alpha chain CDR sequence selected from the group consisting of TCR alpha chain CDR sequences listed in Table 2;
- and/or
- b) a TCR beta chain CDR sequence selected from the group consisting of TCR beta chain CDR sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M;
- 9) comprises:
- a) a TCR alpha chain variable (Vα) domain sequence selected from the group consisting of TCR Vα domain sequences listed in Table 2;
- and/or
- b) a TCR beta chain variable (Vβ) domain sequence selected from the group consisting of TCR Vβ domain sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M;
- and/or
- 10) comprises:
- a) a TCR alpha chain sequence selected from the group consisting of TCR alpha chain sequences listed in Table 2;
- and/or
- b) a TCR beta chain sequence selected from the group consisting of TCR beta chain sequences listed in Table 2, wherein the binding protein is capable of binding to a MAGEA1 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5×10−4 M.
-62. (canceled)
-78. (canceled)
A TCR alpha chain and/or beta chain selected from the group consisting of TCR alpha chain and beta chain sequences listed in Table 2.
An isolated nucleic acid molecule i) that hybridizes, under stringent conditions, with the complement of a nucleic acid encoding a polypeptide selected from the group consisting of polypeptide sequences listed in Table 2, ii) a sequence with at least about 80% homology to a nucleic acid encoding a polypeptide selected from the group consisting of the polypeptide sequences listed in Table 2, and/or iii) ii) a sequence with at least about 80% homology to a nucleic acid encoding listed in Table 2, optionally wherein the isolated nucleic acid molecule comprises 1) a TRAV, TRAJ, and/or TRAC gene or fragment thereof selected from the group of TRAV, TRAJ, and TRAC genes listed in Table 2 and/or 2) a TRBV, TRBJ, and/or TRBC gene or fragment thereof selected from the group of TRBV, TRBJ, and TRBC genes listed in Table 2;
- further optionally wherein the nucleic acid is codon optimized for expression in a host cell.
(canceled)
-88. (canceled)
-114. (canceled)
-122. (canceled)
-125. (canceled)
(canceled)
-131. (canceled)
-142. (canceled)
Dependencies are inferred from the claim text.