Composition of tumor-associated peptides and related anti-cancer vaccine for the treatment of gastric cancer and other cancers
The present invention relates to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. The present invention discloses tumor-associated T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the composition of the peptides of the present invention can be used in vaccine compositions for eliciting anti-tumor immune responses against gastric cancers (GC).
1. A method of identifying a T cell receptor specific for a complex of a peptide and an MHC molecule, comprising:
(a) providing a complex of a peptide and an MHC molecule, wherein the peptide consists of a sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:10, SEQ ID NO:20, and SEQ ID NO:24, wherein the MHC molecule is HLA-A*024;
(b) providing a negative control complex comprising the MHC molecule;
(c) isolating CD8+ enriched PBMCs comprising a T cell bearing a T cell receptor, wherein the T cell receptor is expressed on the surface of the T cell;
(d) detecting a binding between the complex of (a) and the T cell receptor of (c) and a binding between the complex of (b) and the T cell receptor of (c); and
(e) identifying the T cell receptor specific for the complex of (a) when the percent binding between the complex of (a) and the T cell receptor of (c) in the isolated CD8+ T cells is at least 10 times greater than the percent binding between the complex of (b) and the T cell receptor of (c).
2. The method of claim 1 , wherein the specific binding between the complex of (a) and the T cell receptor of (c) induces a T-cell response in the T cell.
3. The method of claim 2 , wherein the T cell response is selected from the group consisting of proliferation, lysis of peptide-presenting target cells that express complexes of HLA-A*024 and a peptide consisting of the sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10, SEQ ID NO: 20 and SEQ ID NO: 24, secretion of cytokines and secretion of effector molecules.
4. The method of claim 1 , wherein the percent binding is determined by flow cytometry analysis.