Vaccinal strategy
View Patent ↗The present invention relates to the prevention and treatment of disease like cancer. The inventors have previously characterized MELOE-1 antigen as an IRES dependent, melanoma specific translation product from a lncRNA mainly transcribed in the melanocytic lineage. MELOE-1 contains numerous class II epitopes and one HLA-A*0201-restricted CD8 epitope eliciting a frequent repertoire of high avidity T cells. They designed various synthetic long peptide (SLPs) comprising a CD4 epitope coupled to the CD8 epitope by a serie of linkers of 4 to 6 aa and studied the efficacy of T cell clone activation by SLP-loaded DC in vitro. Particularly, they evaluated the ability of a few selected SLPs to stimulate specific T cells proliferation of PBL from healthy donors in vitro and finally, they explored the vaccination potential of their best SLP candidate in vivo in an HLA*A0201/HLA-DRB0101 transgenic mouse. Thus, the present invention relates a SLP comprising a CD4 class II peptide linked to a CD8 class I peptide by a specific linker and its use in the treatment of disease like cancers.
1. A synthetic long peptide (SLP) comprising a CD4 class II peptide linked to a CD8 class I peptide by a peptidic linker,
wherein the peptidic linker is selected from the group consisting of the amino acid sequences LLSVG (SEQ ID NO:8), LLSVGG (SEQ ID NO:9) and LLSVGA (SEQ ID NO:191), and
wherein the CD4 class II peptide is linked at its C-terminal position to the peptidic linker and the CD8 class I peptide is linked at its N-terminal position to the peptidic linker, and
wherein the CD4 class II peptide and/or the CD8 class I peptide consists of a contiguous amino acid sequence selected from the group consisting of: SEQ ID NO:15 to 64, SEQ ID NO: 121 to 144 and SEQ ID NO:148 to 158.
2. A nucleic acid sequence encoding an SLP according to claim 1 .
3. A vaccine composition comprising an SLP according to claim 1 .
4. A T lymphocyte that recognizes specifically a SLP according to claim 1 .
5. A method for treating cancer, infectious diseases, inflammatory diseases or auto-immune diseases by in a patient in need thereof comprising,
administering to the patient the SLP according to claim 1 or a nucleic acid encoding the SLP.
6. The method of claim 5 , wherein the SLP is administered in a vaccine composition.
7. The method of claim 5 , wherein the cancer is melanoma.
8. The SLP of claim 1 , wherein the peptidic linker is SEQ ID NO:8.
9. The SLP of claim 1 , wherein the peptidic linker is SEQ ID NO:9.
10. The SLP of claim 1 , wherein the peptidic linker is SEQ ID NO:191.
11. A synthetic long peptide (SLP) comprising a CD4 class II peptide linked to a CD8 class I peptide by a peptidic linker,
wherein the peptidic linker is selected from the group consisting of the amino acid sequences LLSV (SEQ ID NO:4), LLSVG (SEQ ID NO:8) and LLSVGG (SEQ ID NO:9), and
wherein the CD4 class II peptide is linked at its C-terminal position to the peptidic linker and the CD8 class I peptide is linked at its N-terminal position to the peptidic linker, and
wherein the SLP has an amino acid sequence selected from the group consisting of SEQ ID NO:68, SEQ ID NO:87, SEQ ID NO: 181 and SEQ ID NO: 182.
12. A synthetic long peptide (SLP) comprising a CD4 class II peptide linked to a CD8 class I peptide by a peptidic linker having the amino acid sequence identity of LLSVGG (SEQ ID NO:9), and
wherein the CD4 class II peptide is linked at its C-terminal position to the peptidic linker and the CD8 class I peptide is linked at its N-terminal position to the peptidic linker, and
wherein the SLP has an amino acid sequence selected from the group consisting of SEQ ID NO:68, SEQ ID NO:87, SEQ ID NO:96, SEQ ID NO: 181 and SEQ ID NO: 182.