Claudin-6-specific immunoreceptors and t cell epitopes
The present invention provides Claudin-6-specific immunoreceptors (T cell receptors and artificial T cell receptors (chimeric antigen receptors; CARs)) and T cell epitopes which are useful for immunotherapy.
1. An artificial T cell receptor which comprises a binding domain for claudin-6 (CLDN6), wherein the binding domain for CLDN6 comprises the complementary-determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region (VH) according to SEQ ID NO: 32 and the complementary-determining regions CDR1, CDR2 and CDR3 of the light chain variable region (VL) according to SEQ ID NO: 39, wherein the artificial T cell receptor comprises an amino acid sequence according to SEQ ID NO: 46.
2. An artificial T cell receptor which comprises a binding domain for claudin-6 (CLDN6), wherein the binding domain for CLDN6 comprises the complementary-determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region (VH) according to SEQ ID NO: 32 and the complementary-determining regions CDR1, CDR2 and CDR3 of the light chain variable region (VL) according to SEQ ID NO: 39, wherein the artificial T cell receptor comprises an amino acid sequence which is at least 95% identical to the amino acid sequence of SEQ ID NO: 46.
3. The artificial T cell receptor of claim 2 , wherein said heavy chain variable region (VH) and the corresponding light chain variable region (VL) are connected via a peptide linker, preferably a peptide linker comprising the amino acid sequence (GGGGS)3.
4. The artificial T cell receptor of claim 2 , wherein the binding domain for CLDN6 comprises a VH comprising an amino acid sequence represented by SEQ ID NO: 32.
5. The artificial T cell receptor of claim 2 , wherein the binding domain for CLDN6 comprises a VL comprising an amino acid sequence represented by SEQ ID NO: 39.
6. The artificial T cell receptor of claim 2 , wherein the binding domain for CLDN6 comprises a VH comprising an amino acid sequence represented by SEQ ID NO: 32 and a VL comprising an amino acid sequence represented by SEQ ID NO: 39.
7. The artificial T cell receptor of claim 2 , wherein the binding domain for CLDN6 comprises an amino acid sequence represented by SEQ ID NO: 40.
8. The artificial T cell receptor of claim 2 which comprises a transmembrane domain.
9. The artificial T cell receptor of claim 2 which comprises a T cell signaling domain.
10. The artificial T cell receptor of claim 9 , wherein the T cell signaling domain comprises the endodomain of CD3-zeta or a functional fragment thereof.
11. The artificial T cell receptor of claim 2 which comprises a signal peptide which directs the nascent protein into the endoplasmic reticulum.
12. An artificial T cell receptor which comprises a binding domain for claudin-6 (CLDN6), a transmembrane domain, and a T cell signaling domain,
wherein the binding domain for CLDN6 comprises the complementary-determining regions CDR1, CDR2 and CDR3 of the heavy chain variable region (VH) according to SEQ ID NO: 32 and the complementary-determining regions CDR1, CDR2 and CDR3 of the light chain variable region (VL) according to SEQ ID NO: 39, wherein the transmembrane domain is a transmembrane domain as shown in SEQ ID NO: 44, and wherein the T cell signaling domain is a T cell signaling domain as shown in SEQ ID NO: 45.