Multi-epitope peptide-loaded dendritic cell immunotherapy for cancer
Peptides of from about 7 to about 50 amino acid residues in length that have epitopes that bind to more than one HLA class II protein and stimulate CD4+ T cells for treatment of cancer from one of three serine proteases overexpressed in ovarian cancer and other cancers—stratum corneum chymotryptic enzyme, matriptase, and hepsin—are described. Since the peptides bind to more than one HLA class II protein variant, they can be used to treat cancer in most patients of a population having a variety of HLA class II alleles. The peptides can be loaded onto autologous dendritic cells of a cancer patient and infused into the patient to activate a CD4+ and CD8+ T cell response that recognizes tumor cells expressing the peptide antigen.
1. A composition comprising:
purified dendritic cells loaded ex vivo with a purified peptide of 7-50 amino acid residues comprising an antigenic matriptase sequence of 7-50 amino acid residues;
wherein when the purified peptide is contacted with dendritic cells to generate peptide-loaded dendritic cells and the peptide-loaded dendritic cells are contacted with T cells, the peptide-loaded dendritic cells amplify CD4+ T cells (helper T cells) that recognize the matriptase sequence.
2. The composition of claim 1 wherein when the purified peptide is contacted with dendritic cells to generate peptide-loaded dendritic cells and the peptide-loaded dendritic cells are contacted with T cells, the peptide-loaded dendritic cells amplify CD8+ T cells (cytotoxic T lymphocytes, CTL) that recognize the matriptase sequence.
3. The composition of claim 2 wherein the amplified CD8+ T cells kill autologous cancer cells expressing matriptase.
4. The composition of claim 1 wherein the peptide can be used with dendritic cells to activate CD4+ T cells from at least two donors with no HLA class II alleles in common.
5. The composition of claim 1 wherein the purified peptide comprises SEQ ID NO:4 (residues 170-204 of SEQ ID NO:3), SEQ ID NO:5 (residues 273-296 of SEQ ID NO:3), SEQ ID NO:6 (residues 308-343 of SEQ ID NO:3), or SEQ ID NO:7 (residues 379-399 of SEQ ID NO:3.
6. A composition of matter comprising:
purified dendritic cells loaded ex vivo with a purified peptide comprising an antigenic matriptase sequence of at least 7 amino acid residues;
wherein when the purified peptide is contacted with dendritic cells to generate peptide-loaded dendritic cells and the peptide-loaded dendritic cells are contacted with T cells, the peptide-loaded dendritic cells amplify CD4+ T cells (helper T cells) that recognize the matriptase sequence.
7. The composition of matter of claim 6 wherein the peptide can be used with dendritic cells to activate CD4+ T cells from at least two donors with no HLA class II alleles in common.
8. The composition of matter of claim 6 wherein the purified peptide is a purified peptide of 50 or fewer amino acid residues comprising SEQ ID NO:4 (residues 170-204 of SEQ ID NO:3), SEQ ID NO:5 (residues 273-296 of SEQ ID NO:3), SEQ ID NO:6 (residues 308-343 of SEQ ID NO:3), or SEQ ID NO:7 (residues 379-399 of SEQ ID NO:3.