XBP1, CD138, and CS1 peptides, pharmaceutical compositions that include the peptides, and methods of using such peptides and compositions
The disclosure features, inter alia, immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof). The peptides can be used in a variety of methods such as methods for inducing an immune response, methods for producing an antibody, and methods for treating a cancer (e.g., breast cancer, colon cancer, pancreatic cancer, a blood cancer, e.g., leukemia or a plasma cell disorder such as multiple myeloma or Waldenstrom's macroglobulinemia). The peptides (and pharmaceutical compositions comprising the peptides) can be used, e.g., in a method of treating a precancerous condition such as smoldering multiple myeloma. The peptides can also be included in MHC molecule multimer compositions and used in, e.g., methods for detecting a T cell in a population of cells.
1. A method for inducing an immune response in a subject having estrogen receptor negative breast cancer, colon cancer, pancreatic cancer, or leukemia, the method comprising delivering to the subject a composition comprising a non spliced XBP1 peptide of 35 amino acids or less in length comprising the amino acid sequence of SEQ ID NO:6, a spliced XBP1 peptide of 35 amino acids or less in length and comprising the amino acid sequence of SEQ ID NO:10, and a CD138 peptide of 35 amino acids or less in length and comprising the amino acid sequence of SEQ ID NO:12.
2. The method of claim 1 , further comprising, after delivering the composition to the subject, determining if an immune response occurred in the subject.
3. The method of claim 1 , wherein the subject is a human.
4. The method of claim 1 , comprising administering the composition in combination with an additional treatment selected from one or more of a chemotherapeutic agent, ionizing radiation, or an immunotherapy agent.
5. The method of claim 1 , further comprising administering to the subject one or more immune stimulating agents and/or one or more immune modulating agents.
6. The method of claim 5 , wherein the one or more immune stimulating agents is selected from an adjuvant comprising carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA; an adjuvant comprising a water-and-oil emulsion; and an adjuvant comprising a protein.
7. The method of claim 6 , wherein the adjuvant comprising carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA is poly ICLC.
8. The method of claim 6 , wherein the adjuvant comprising a water-and-oil emulsion is montanide.
9. The method of claim 6 , wherein the adjuvant comprising a protein is a cytokine, GCSF, or GM-CSF.
10. The method of claim 5 , wherein the one or more immune modulating agents is an antibody which activates the immune system.
11. The method of claim 10 , wherein the antibody which activates the immune system is an anti-CTLA4 antibody, an anti-PD-1 antibody, or an anti-PDL-1 antibody.
12. The method of claim 5 , wherein the one or more immune modulating agents is an adjuvant.
13. The method of claim 12 , wherein the adjuvant is a thalidomide derivative.
14. The method of claim 13 , wherein the adjuvant is lenalidomide.
15. The method of claim 1 , wherein the composition further comprises a CS-1 peptide of 35 amino acids or less in length comprising the amino acid sequence of SEQ ID NO:16.
16. The method of claim 15 , wherein the CS-1 peptide consists of the amino acid sequence of SEQ ID NO:16.
17. The method of claim 15 , wherein the non-spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:6, the spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:10, the CD138 peptide consists of the amino acid sequence of SEQ ID NO:12, and the CS-1 peptide consists of the amino acid sequence of SEQ ID NO:16.
18. The method of claim 15 , further comprising determining whether one or more cancer cells expresses XBP1, CD138, or CS1.
19. The method of claim 1 , wherein the non-spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:6.
20. The method of claim 1 , wherein the spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:10.
21. The method of claim 1 , wherein the CD138 peptide consists of the amino acid sequence of SEQ ID NO:12.
22. The method of claim 1 , wherein the breast cancer is HER-2 positive breast cancer, HER-2 negative breast cancer, triple negative breast cancer, or inflammatory breast cancer.
23. The method of claim 1 , wherein the subject expresses HLA-A2.
24. A method for treating a subject having estrogen receptor negative breast cancer, colon cancer, pancreatic cancer, or leukemia, the method comprising administering to the subject a composition comprising a non spliced XBP1 peptide of 35 amino acids or less in length comprising the amino acid sequence of SEQ ID NO:6, a spliced XBP1 peptide of 35 amino acids or less in length and comprising the amino acid sequence of SEQ ID NO:10, and a CD138 peptide of 35 amino acids or less in length and comprising the amino acid sequence of SEQ ID NO:12.
25. The method of claim 24 , wherein the breast cancer is HER-2 positive breast cancer, HER-2 negative breast cancer, triple negative breast cancer, or inflammatory breast cancer.
26. The method of claim 24 , further comprising, after delivering the composition to the subject, determining if an immune response occurred in the subject.
27. The method of claim 24 , wherein the subject is a human.
28. The method of claim 24 , comprising administering the composition in combination with an additional treatment selected from one or more of a chemotherapeutic agent, ionizing radiation, or an immunotherapy agent.
29. The method of claim 24 , further comprising administering to the subject one or more immune stimulating agents and/or one or more immune modulating agents.
30. The method of claim 29 , wherein the one or more immune stimulating agents is selected from an adjuvant comprising carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA; an adjuvant comprising a water-and-oil emulsion; and an adjuvant comprising a protein.
31. The method of claim 30 , wherein the adjuvant comprising carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA is poly ICLC.
32. The method of claim 30 , wherein the adjuvant comprising a water-and-oil emulsion is montanide.
33. The method of claim 30 , wherein the adjuvant comprising a protein is a cytokine, GCSF, or GM-CSF.
34. The method of claim 29 , wherein the one or more immune modulating agents is selected from an adjuvant or an antibody which activates the immune system.
35. The method of claim 34 , wherein the antibody which activates the immune system is an anti-CTLA4 antibody, an anti-PD-1 antibody, or an anti-PDL-1 antibody.
36. The method of claim 34 , wherein the adjuvant is a thalidomide derivative.
37. The method of claim 36 , wherein the adjuvant is lenalidomide.
38. The method of claim 24 , wherein the composition further comprises a CS-1 peptide of 35 amino acids or less in length comprising the amino acid sequence of SEQ ID NO:16.
39. The method of claim 38 , wherein the CS-1 peptide consists of the amino acid sequence of SEQ ID NO:16.
40. The method of claim 38 , wherein the non-spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:6, the spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:10, the CD138 peptide consists of the amino acid sequence of SEQ ID NO:12, and the CS-1 peptide consists of the amino acid sequence of SEQ ID NO:16.
41. The method of claim 38 , further comprising determining whether one or more cancer cells expresses XBP1, CD138, or CS1.
42. The method of claim 24 , wherein the non-spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:6.
43. The method of claim 24 , wherein the spliced XBP1 peptide consists of the amino acid sequence of SEQ ID NO:10.
44. The method of claim 24 , wherein the CD138 peptide consists of the amino acid sequence of SEQ ID NO:12.
45. The method of claim 24 , wherein the subject expresses HLA-A2.
46. A method for treating a human subject having triple negative breast cancer, the method comprising administering to the subject a composition comprising a non-spliced XBP1 peptide that consists of the amino acid sequence of SEQ ID NO:6, a spliced XBP1 peptide that consists of the amino acid sequence of SEQ ID NO:10, and a CD138 peptide that consists of the amino acid sequence of SEQ ID NO:12.