Combination of ny-eso-1 specific t cell receptors and chimeric co-stimulatory receptors
AssigneeMedigene Immunotherapies GmbH
InventorsMaja BÜRDEK, Kathrin MUTZE, Petra PRINZ, Angelika HELMBRECHT
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Abstract
The present invention refers immune cells expressing a TCR and a co-stimulatory. In particular, the invention refers to immune cells expressing a (i) T cell receptor (TCR) specific for a TCR specific for NY-ESO-1 peptide SLLMWITQC and (ii) a chimeric co-stimulatory receptor comprising an extracellular domain derived from PD-1 (CD279) and an intracellular domain derived from 4-1BB (CD137).
Claims35
The target specific immune cell, wherein the target specific immune cell expresses
- (A) a NY-ESO-1/LAGE-1 specific TCR, comprising
- a TCR α chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:
- 35, a CDR 2 having the amino acid sequence of SEQ ID NO:
- 36 and a CDR 3 having the sequence of SEQ ID NO:
- 37;
- and
- a TCR β chain comprising a CDR1 having the amino acid sequence of SEQ ID NO:
- 38, a CDR 2 having the amino acid sequence of SEQ ID NO:
- 39 and a CDR 3 having the sequence of SEQ ID NO:
- 40;
- (B) a chimeric co-stimulatory receptor comprising
- an extracellular domain containing a polypeptide derived from PD-1,
- a transmembrane domain, and
- an intracellular domain containing a polypeptide derived from 4-1BB.
The target specific immune cell according to claim 2, wherein the chimeric co-stimulatory receptor comprises
- an extracellular domain containing a extracellular domain derived from PD-1,
- a transmembrane domain derived from PD-1, and
- an intracellular domain containing a intracellular domain derived from 4-1BB.
The target specific immune cell according to claim 3, wherein the extracellular domain derived from PD-1 comprises an amino acid sequence with up to 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions compared to the extracellular domain derived from PD-1 as set out in SEQ ID NO:
- 28.
The target specific immune cell according to any one of the preceding claims, wherein the intracellular domain derived from 4-1BB comprises an amino acid sequence with up to 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions compared to the intercellular domain derived from 4-1BB as set out in SEQ ID NO:
- 32.
The target specific immune cell according to any one of the preceding claims, wherein the extracellular domain derived from PD-1 comprises the sequence of SEQ ID NO:
- 28 and wherein the intracellular domain derived from 4-1BB comprises the sequence of SEQ ID NO:
- 32.
The target specific immune cell according to any one of the preceding claims, preferably wherein the chimeric co-stimulatory receptor comprises the sequence of SEQ ID NO:
- 26.
The target specific immune cell according to any one of the preceding claims, wherein the target specific immune cell is a lymphocyte.
The target specific immune cell according to any one of the preceding claims, wherein the target specific immune cell is a T cell.
The target specific immune cell according to anyone of the preceding claims, wherein the TCR comprises a variable TCR α region having an amino acid sequence which is at least 80% identical to SEQ ID NO:
- 41 and a variable TCR β region having an amino acid sequence which is at least 80% identical to SEQ ID NO:
- 42.
The target specific immune cell according to anyone of the preceding claims, wherein the TCR comprises a variable TCR α region having the amino acid sequence of SEQ ID NO:
- 41 and a variable TCR β region having the amino acid sequence of SEQ ID NO:
- 42.
The target specific immune cell according to anyone of the preceding claims, wherein the TCR is capable of binding to a NY-ESO peptide having the amino acid sequence set out in SEQ ID NO:
- 34 or a portion thereof, preferably its HLA-A2 bound form.
The target specific immune cell according to anyone of the preceding claims, wherein the HLA-A2 is an HLA-A*02:01, HLA-A*02:02, HLA-A*02:04 or HLA-A*02:09 encoded molecule preferably HLA-A*2:01 encoded molecule.
Dependencies are inferred from the claim text.