Immunogenic peptides specific to BCMA and TACI antigens
This disclosure relates to immunogenic peptides that are specific to B-cell maturation antigen (BCMA) and Transmembrane activator and CAML interactor (TACI), and methods of use thereof.
1. A peptide comprising:
(a) an amino acid sequence set forth in any one of SEQ ID NOs: 13-17; or
(b) a first amino acid sequence consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 1-17; and a second amino acid sequence that is heterologous to the first amino acid sequence; wherein the second amino acid sequence that is heterologous to the first amino acid sequence comprises: (i) a purification tag, (ii) a detectable marker, (iii) an immunoglobulin molecule or a portion thereof comprising a heavy chain constant region, (iv) a therapeutic or immune-stimulating polypeptide, (v) a carrier, or (vi) a transportation sequence.
2. A composition comprising the peptide of claim 1 and a second agent.
3. The composition of claim 2 , wherein the second agent is: an immune stimulatory agent, a T helper epitope, an adjuvant, a toll like receptor-3 ligand, interferon alfa (IFNα), interferon gamma (IFNγ), an anti-0X40 antibody, an anti-glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) antibody, or Granulocyte-macrophage colony-stimulating factor (GM-CSF).
4. A pharmaceutical composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.
5. A method of inducing an immune response against BCMA- and/or TACI-expressing cancer cells in a human subject in need thereof, the method comprising administering to the human subject the peptide of claim 1 .
6. A method of treating a human subject having multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or smoldering multiple myeloma, the method comprising administering to the human subject the peptide of claim 1 .
7. A method of generating and/or proliferating BCMA-specific cytotoxic T cells, the method comprising
contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a peptide comprising the amino acid sequence set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
8. A method of generating TACI-specific cytotoxic T cells, the method comprising
contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a peptide comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15-17.
9. A method of killing a target cell, the method comprising
(a) contacting the target cell with one or more BCMA-specific cytotoxic T cells, wherein the target cell expresses or overexpresses BCMA, and expresses HLA-A, wherein the BCMA-specific cytotoxic T cells are obtained by contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a first peptide comprising the amino acid sequence set forth in SEQ ID NO: 13 or SEQ ID NO: 14; or
(b) contacting the target cell with one or more TACI-specific cytotoxic T cells, wherein the target cell expresses or overexpresses TACI, and expresses HLA-A, wherein the TACI-specific cytotoxic T cells are obtained by contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a second peptide comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-17.
10. A method of treating a human subject having multiple myeloma a cancer, the method comprising
administering a plurality of BCMA-specific cytotoxic T cells or TACI-specific cytotoxic T cells to the human subject, wherein the BCMA-specific cytotoxic T cells are obtained by contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a first peptide comprising the amino acid sequence set forth in SEQ ID NO: 13 or SEQ ID NO: 14; wherein the TACI-specific cytotoxic T cells are obtained by contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a second peptide comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-17.
11. A process comprising,
(a) obtaining bone marrow derived mononuclear cells from a subject;
(b) culturing the mononuclear cells in vitro under a condition in which mononuclear cells become adherent to a culture vessel;
(c) selecting adherent mononuclear cells;
(d) culturing the adherent mononuclear cells in the presence of one or more cytokines under a condition in which the cells differentiate into antigen present cells; and
(e) contacting the antigen presenting cells with the peptide of claim 1 , thereby generating antigen presenting cells that present the peptide on a major histocompatibility complex (MHC) molecule.
12. A method of identifying a T cell antigen receptor sequence for BCMA, the method comprising
(a) generating and/or proliferating BCMA-specific cytotoxic T cells, wherein the method of generating and/or proliferating BCMA-specific cytotoxic T cells comprises contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a peptide comprising the amino acid sequence set forth in SEQ ID NO: 13 or SEQ ID NO: 14; and
(b) determining the T cell antigen receptor sequence for BCMA in the BCMA-specific cytotoxic T cells.
13. A method of identifying a T cell antigen receptor sequence for TACI, the method comprising
(a) generating and/or proliferating TACI-specific cytotoxic T cells wherein the method of generating and/or proliferating TACI-specific cytotoxic T cells comprises contacting one or more cytotoxic T cells with one or more antigen presenting cells pulsed with a peptide comprising an amino acid sequence set forth in any one of SEQ ID NOs: 15-17; and
(b) determining the T cell antigen receptor sequence for TACI in the TACI-specific cytotoxic T cells.
14. The peptide of claim 1 , which comprises the amino acid sequence set forth in any one of SEQ ID NOs:13-17.
15. The peptide of claim 1 , which consists of the amino acid sequence set forth in any one of SEQ ID NOs:13-17.
16. The peptide of claim 1 , which comprises the amino acid sequence set forth SEQ ID NO:13.
17. The peptide of claim 1 , which comprises the amino acid sequence set forth SEQ ID NO:14.
18. The peptide of claim 1 , which comprises the amino acid sequence set forth SEQ ID NO:15.
19. The peptide of claim 1 , which comprises the amino acid sequence set forth SEQ ID NO:16.
20. The peptide of claim 1 , which comprises the amino acid sequence set forth SEQ ID NO:17.
21. The peptide of claim 1 , which comprises the first amino acid sequence consisting of an amino acid sequence set forth in any one of SEQ ID NOs: 1-17; and the second amino acid sequence that is heterologous to the first amino acid sequence; wherein the second amino acid sequence that is heterologous to the first amino acid sequence comprises: (i) a purification tag, (ii) a detectable marker, (ii) an immunoglobulin molecule or a portion thereof comprising a heavy chain constant region, (iii) a therapeutic or immune-stimulating polypeptide, (iv) a carrier protein, or (v) a transportation sequence.
22. The peptide of claim 1 , which is 9 to 30 amino acids in length.
23. A pharmaceutical composition comprising the peptide of claim 15 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the peptide of claim 16 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising the peptide of claim 17 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising the peptide of claim 18 and a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising the peptide of claim 19 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the peptide of claim 20 and a pharmaceutically acceptable carrier.
29. The method of claim 6 , wherein the human subject has MGUS or smoldering multiple myeloma.
30. The method of claim 6 , wherein the human subject has multiple myeloma.
31. A method of inducing an immune response against BCMA- and/or TACI-expressing cancer cells in a human subject in need thereof, the method comprising administering to the human subject a peptide of claim 14 .
32. A method of inducing an immune response against BCMA- and/or TACI-expressing cancer cells in a human subject in need thereof, the method comprising administering to the human subject a peptide of claim 15 .
33. A method of treating a human subject having multiple myeloma, MGUS, or smoldering multiple myeloma, the method comprising administering to the human subject the peptide of claim 14 .
34. A method of treating a human subject having multiple myeloma, MGUS, or smoldering multiple myeloma, the method comprising administering to the human subject the peptide of claim 15 .
35. The method of claim 33 , wherein the human subject has MGUS or smoldering multiple myeloma.
36. The method of claim 34 , the human subject has MGUS or smoldering multiple myeloma.
37. The method of claim 33 , wherein the human subject has multiple myeloma.
38. The method of claim 34 , wherein the human subject has multiple myeloma.