T cell receptor
AssigneeAdaptimmune Limited
InventorsWilliam Lawrance, Philip Clive Simister
Life of this patent
Estimating the term…
Abstract
The disclosure relates to T cell receptors (TCRs) that can bind to HLA-A*02 restricted peptides derived from PRAME. The disclosure also relates to complexes comprising these TCRs, nucleic acids and vectors encoding these TCRs, or portions thereof, cells comprising these TCRs, pharmaceutical compositions, and methods of using these TCRs to treat diseases, such as cancer.
Claims29
A T cell receptor (TCR) that binds to a complex comprising SEQ ID NO:
- 1 and HLA-A*02, and comprises:
- (a) a TCR alpha chain variable domain that comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO:
- 17;
- and
- (b) a TCR beta chain variable domain that comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO:
- 29.
The TCR of any one of the preceding claims, wherein:
- (i) the TCR alpha chain variable domain comprises a CDR1 that comprises SEQ ID NO:
- 8, 9, 10, 11, 12, 13 or 14;
- (ii) the TCR alpha chain variable domain comprises a CDR2 that comprises SEQ ID NO:
- 15;
- (iii) the TCR alpha chain variable domain comprises a CDR3 that comprises SEQ ID NO:
- 16;
- (iv) the TCR beta chain variable domain comprises a CDR1 that comprises SEQ ID NO:
- 24;
- (v) the TCR beta chain variable domain comprises a CDR2 that comprises SEQ ID NO:
- 25, 26 or 27;
- and/or
- (vi) the TCR beta chain variable domain comprises a CDR3 that comprises SEQ ID NO:
- 28.
The TCR of any one of the preceding claims, wherein the TCR alpha chain variable domain comprises:
- (i) a CDR1 that comprises SEQ ID NO:
- 8, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- (ii) a CDR1 that comprises SEQ ID NO:
- 9, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- (iii) a CDR1 that comprises SEQ ID NO:
- 10, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- (iv) a CDR1 that comprises SEQ ID NO:
- 11, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- (v) a CDR1 that comprises SEQ ID NO:
- 12, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- (vi) a CDR1 that comprises SEQ ID NO:
- 13, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16;
- or
- (vii) a CDR1 that comprises SEQ ID NO:
- 14, a CDR2 that comprises SEQ ID NO:
- 15, and a CDR3 that comprises SEQ ID NO:
- 16.
The TCR of any one of the preceding claims, wherein the TCR alpha chain variable domain comprises SEQ ID NO:
- 17, 18, 19, 20, 21, 22 or 23.
The TCR of any one of the preceding claims, wherein the TCR beta chain variable domain comprises:
- (i) a CDR1 that comprises SEQ ID NO:
- 24, a CDR2 that comprises SEQ ID NO:
- 25, and a CDR3 that comprises SEQ ID NO:
- 28;
- (ii) a CDR1 that comprises SEQ ID NO:
- 24, a CDR2 that comprises SEQ ID NO:
- 26, and a CDR3 that comprises SEQ ID NO:
- 28;
- or
- (iii) a CDR1 that comprises SEQ ID NO:
- 24, a CDR2 that comprises SEQ ID NO:
- 27, and a CDR3 that comprises SEQ ID NO:
- 28.
The TCR of any one of the preceding claims, wherein the TCR beta chain variable domain comprises SEQ ID NO:
- 29, 20 or 31.
The TCR of any one of the preceding claims, wherein:
- (i) the TCR alpha chain variable domain comprises SEQ ID NO:
- 17 and the TCR beta chain variable domain comprises SEQ ID NO:
- 29;
- (ii) the TCR alpha chain variable domain comprises SEQ ID NO:
- 17 and the TCR beta chain variable domain comprises SEQ ID NO:
- 30;
- (iii) the TCR alpha chain variable domain comprises SEQ ID NO:
- 17 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- (iv) the TCR alpha chain variable domain comprises SEQ ID NO:
- 18 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- (v) the TCR alpha chain variable domain comprises SEQ ID NO:
- 19 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- (vi) the TCR alpha chain variable domain comprises SEQ ID NO:
- 20 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- (vii) the TCR alpha chain variable domain comprises SEQ ID NO:
- 21 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- (viii) the TCR alpha chain variable domain comprises SEQ ID NO:
- 22 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31;
- or
- (ix) the TCR alpha chain variable domain comprises SEQ ID NO:
- 23 and the TCR beta chain variable domain comprises SEQ ID NO:
- 31.
The TCR of any one of the preceding claims, wherein the TCR comprises a TCR alpha chain constant domain and/or a TCR beta chain constant domain.
The TCR of any one of the preceding claims, wherein the TCR is an alpha-beta heterodimer comprising:
- (a) a TCR alpha chain comprising (i) the TCR alpha chain variable domain and (ii) a TCR alpha chain constant domain;
- and
- (b) a TCR beta chain comprising (i) the TCR beta chain variable domain and (ii) a TCR beta chain constant domain.
The TCR of any one of the preceding claims, wherein:
- the TCR is a single chain TCR of the structure Vα-L-Vβ, Vβ-L-Vα, Vα-Cα-L-Vβ, or Vα-L-Vβ-Cβ;
- and wherein Vα is the TCR alpha chain variable domain, Vβ is the TCR beta chain variable domain, Cα is TCR alpha chain constant domain, Cβ is a TCR beta chain constant domain, and L is a linker sequence.
A complex comprising (a) a TCR of any one of the preceding claims, and (b) a detectable label, a therapeutic agent or a pharmacokinetic modifying moiety.
Dependencies are inferred from the claim text.