MHC class II restricted T cell epitopes from the cancer antigen, NY ESO-1
The present invention discloses the identification and isolation of novel MHC class II epitopes derived from the cancer antigen, NY ESO-1. The novel MHC class II epitopes from NY-EsO-1 are recognized by CD4 + T lymphocytes in an HLA class II restricted manner, in particular HLA-DR or HLA-DP restricted. The products of the gene are promising candidates for immunotherapeutic strategies for the prevention, treatment and diagnosis of patients with cancer.
1. A recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a peptide comprising Xaa 1 ITQXaa 2 FXaa 3 PXaa 4 (SEQ ID NO: 51), wherein Xaa 1 is Trp, Xaa 2 is Cys, Xaa 3 is Leu, Xaa 4 represents at least one amino acid residue, and wherein peptide consists of from 9 to 30 amino acid residues and the peptide is immunologically recognized by HLA-DP restricted CD4 + T lymphocytes.
2. The recombinant expression vector of claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 52-58 and 62-64.
3. A host cell comprising the recombinant expression vector of claim 1 .
4. A recombinant virus comprising the recombinant expression vector of claim 1 .
5. A method of producing a recombinant HLA-DP restricted, CD4 + T cell epitope of NY-ESO-1, the method comprising:
(a) transferring the recombinant expression vector of claim 1 into a host cell;
(b) culturing the host cell under conditions sufficient for expression of the peptide; and
(c) harvesting the peptide.
6. A method of making the recombinant expression vector of claim 1 , the method comprising incorporating a nucleic acid into a recombinant expression vector, wherein the nucleic acid sequence is operatively linked with a promoter and comprises a nucleotide sequence encoding a peptide comprising Xaa 1 ITQXaa 2 FXaa 3 PXaa 4 (SEQ ID NO: 51), wherein Xaa 1 is Trp, Xaa 2 is Cys, Xaa 3 is Leu, Xaa 4 represents at least amino acid residue, and wherein peptide consists of from 9 to 30 amino acid residues.
7. A pharmaceutical composition comprising the virus of claim 4 alone or in combination with an exogenous immunostimulatory molecule, chemotherapy drug, antibiotic, antifungal drug, antiviral drug or combination thereof and a pharmaceutically acceptable carrier.
8. A nucleic acid construct comprising the recombinant expression vector of claim 1 , wherein the recombinant expression vector further comprises at least one nucleotide sequence encoding a target antigen or target epitope thereof.
9. A pharmaceutical composition comprising the vector according to claim 1 and a pharmaceutically acceptable carrier.
10. The nucleic acid construct of claim 8 , wherein the target antigen is selected from the group consisting of TRP2, GP-100, TP, an HIV antigen, gp120, and a malaria antigen.
11. The recombinant expression vector of claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 54.
12. The host cell of claim 3 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 54.
13. The recombinant virus according to claim 4 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 54.
14. The pharmaceutical composition of claim 7 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 54.
15. The pharmaceutical composition of claim 9 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 54.