Target CA125 peptides for cancer immunotherapy
View Patent ↗TADG-12 and CA125 are two proteins expressed with high specificity in ovarian cancer tumors. They thus would be potential antigens for immunotherapy in ovarian cancer. The invention is based on the discovery of peptides in TADG-12 and CA125 that can be used to induce an autologous T cell response that lyses ovarian cancer cells expressing TADG-12 or CA125. The peptides are contacted with dendritic cells in vitro to generate peptide-loaded dendritic cells. The peptide-loaded dendritic cells are contacted with T cells in vitro to amplify CD8+ T cells that recognize the peptide. At least one CA125 peptide and at least one TADG-12 peptide were found that amplified CD8+ T cells, even from cancer patients, that lysed autologous CA125-expressing or TADG-12-expressing tumor cells. The peptide-loaded dendritic cells can be administered to a cancer patient to amplify CD8+ T cells in vivo that attack the cancer cells. Alternatively, autologous CD8+ T cells can be amplified ex vivo and then infused into the cancer patient.
1. A method of treating cancer in a patient whose cancer cells express CA125 comprising:
(a) contacting dendritic cells with a purified peptide comprising an HLA-binding CA125 peptide of 7-12 amino acid residues to generate peptide-loaded dendritic cells;
(b) contacting the peptide-loaded dendritic cells with T cells of the cancer patient to amplify CD8+ T cells that recognize the CA125 peptide; and
(c) contacting the amplified CD8+ T cells with CA125-bearing cancer cells in the patient to lyse the CA125-bearing cancer cells;
wherein the CA125 peptide binds to a human class I HLA protein,
wherein when the CA125 peptide is bound to the HLA protein on the surface of 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 that lyse autologous cells expressing CA125 in vivo or in vitro;
wherein the purified peptide comprises SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:11, or SEQ ID NO:12;
wherein the purified peptide is 7 to 50 amino acid residues in length.
2. The method of claim 1 wherein step (a) is performed ex vivo, step (b) comprises infusing the peptide-loaded dendritic cells into the patient to amplify the CD8+ T cells in vivo in the patient, and step (c) occurs in vivo in the patient.
3. The method of claim 1 wherein steps (a) and (b) are performed ex vivo, and step (c) comprises infusing the amplified CD8+ T cells into the patient to contact the CA125-bearing cancer cells in vivo in the patient.
4. The method of claim 1 wherein the purified peptide is 7 to 12 amino acid residues in length.
5. The method of claim 4 wherein the purified peptide is 8 to 10 amino acid residues in length.
6. The method of claim 1 wherein the purified peptide comprises SEQ ID NO:10 (YTLDRDSLYV).
7. The method of claim 1 wherein the CA125-bearing cancer cells are ovarian cancer cells.
8. The method of claim 1 wherein the CA125-bearing cancer cells are lymphoma cells.
9. A method of treating cancer in a patient whose cancer cells express CA125 comprising:
(a) contacting dendritic cells with a purified peptide comprising an HLA-binding CA125 peptide of 7-12 amino acid residues to generate peptide-loaded dendritic cells;
(b) contacting the peptide-loaded dendritic cells with T cells of the cancer patient to amplify CD8+ T cells that recognize the CA125 peptide; and
(c) contacting the amplified CD8+ T cells with CA125-bearing cancer cells in the patient to lyse the CA125-bearing cancer cells;
wherein the CA125 peptide binds to a human class I HLA protein,
wherein when the CA125 peptide is bound to the HLA protein on the surface of 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 that lyse autologous cells expressing CA125 in vivo or in vitro;
wherein the purified peptide comprises at least 7 amino acid residues of SEQ ID NO:10 in the same order and with the spacing as in SEQ ID NO:10;
wherein the purified peptide is 7 to 50 amino acid residues in length.
10. The method of claim 9 wherein the purified peptide comprises at least 8 amino acid residues of SEQ ID NO:10 in the same order and with the spacing as in SEQ ID NO:10.
11. The method of claim 9 wherein the purified peptide comprises at least 9 amino acid residues of SEQ ID NO:10 in the same order and with the spacing as in SEQ ID NO:10.
12. The method of claim 9 wherein step (a) is performed ex vivo, step (b) comprises infusing the peptide-loaded dendritic cells into the patient to amplify the CD8+ T cells in vivo in the patient, and step (c) occurs in vivo in the patient.
13. The method of claim 9 wherein steps (a) and (b) are performed ex vivo, and step (c) comprises infusing the amplified CD8+ T cells into the patient to contact the CA125-bearing cancer cells in vivo in the patient.
14. The method of claim 9 wherein the purified peptide is 7 to 12 amino acid residues in length.
15. The method of claim 9 wherein the purified peptide is 8 to 10 amino acid residues in length.
16. The method of claim 9 wherein the CA125-bearing cancer cells are ovarian cancer cells.
17. The method of claim 9 wherein the CA125-bearing cancer cells are lymphoma cells.