Methods and compositions for identifying prostate cancer or a humoral immune response against prostate cancer
View Patent ↗The present invention relates to prostate cancer markers, compositions comprising such markers, immunoglobulins specific for such markers, and methods of using such markers and/or immunoglobulins to assess an immune response against prostate cancer. An immune response against the markers correlates with an immune response, in particular a humoral immune response, against prostate cancer cells which immune response is preferably associated with prophylaxis of prostate cancer, treatment of prostate cancer, and/or amelioration of at least one symptom associated with prostate cancer.
1. A method for determining whether a subject is likely to respond to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising detecting an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin, wherein detecting the immune response indicates that the subject is likely to respond to said prostate cancer therapy.
2. The method of claim 1 , wherein the subject is a mammal.
3. The method of claim 1 , wherein the subject is a human.
4. The method of claim 1 , wherein the cancer cells are autologous.
5. The method of claim 1 , wherein the cancer cells are allogeneic.
6. The method of claim 1 , wherein the cancer cells are LnCaP cells or PC3 cells.
7. The method of claim 1 , further comprising detecting an immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9, wherein detecting said immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9 indicates that the subject is likely to respond to said prostate cancer therapy.
8. The method of claim 1 , wherein an immune response is detected against HLA-A24.
9. The method of claim 1 , wherein an immune response is detected against OTUB2.
10. The method of claim 1 , wherein an immune response is detected against FLJ14668.
11. The method of claim 1 , wherein an immune response is detected against NNAT.
12. The method of claim 1 , wherein an immune response is detected against cardiolipin.
13. The method of claim 1 , wherein responsiveness to the cancer therapy is measured by decreased serum concentrations of tumor specific markers, increased overall survival time, increased progression-free survival, decreased tumor size, decreased bone metastasis marker response, increased impact on minimal residual disease, increased induction of antibody response to the cancer cells that have been rendered proliferation-incompetent, increased induction of delayed-type-hypersensitivity (DTH) response to injections of autologous tumor, increased induction of T cell response to autologous tumor or candidate tumor-associated antigens, increased impact on circulating T cell and dendritic cell numbers, phenotype, and function, cytokine response, decreased concentrations of prostate-specific antigen (PSA), reduced slope of PSA doubling time, increased PSA doubling time, reduced metastasis as measured by bone scan, increased time to progression, increased survival time as compared to the Halabi nomogram, decreased serum concentrations of ICTP, or decreased concentrations of serum C-reactive protein.
14. The method of claim 1 , wherein the immune response is a humoral immune response.
15. A computer-implemented method for determining whether a subject is likely to respond to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising inputting into a computer memory data indicating whether an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin is detected, inputting into the computer memory a correlation between an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin and a likelihood of responding to said therapy, and determining whether the subject is likely to respond to said therapy.
16. The method of claim 15 , wherein the subject is a mammal.
17. The method of claim 15 , wherein the subject is a human.
18. The method of claim 15 , wherein the cancer cells are autologous.
19. The method of claim 15 , wherein the cancer cells are allogeneic.
20. The method of claim 15 , wherein the cancer cells are LnCaP cells or PC3 cells.
21. The method of claim 15 , further comprising inputting into a computer memory data indicating whether an immune response is detected against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9, inputting into the computer memory a correlation between an immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9, and determining whether the subject is likely to respond to said therapy.
22. The method of claim 15 , wherein an immune response is detected against HLA-A24.
23. The method of claim 15 , wherein an immune response is detected against OTUB2.
24. The method of claim 15 , wherein an immune response is detected against FLJ14668.
25. The method of claim 15 , wherein an immune response is detected against NNAT.
26. The method of claim 15 , wherein an immune response is detected against cardiolipin.
27. The method of claim 15 , wherein responsiveness to the cancer therapy is measured by decreased serum concentrations of tumor specific markers, increased overall survival time, increased progression-free survival, decreased tumor size, decreased bone metastasis marker response, increased impact on minimal residual disease, increased induction of antibody response to the cancer cells that have been rendered proliferation-incompetent, increased induction of delayed-type-hypersensitivity (DTH) response to injections of autologous tumor, increased induction of T cell response to autologous tumor or candidate tumor-associated antigens, increased impact on circulating T cell and dendritic cell numbers, phenotype, and function, cytokine response, decreased concentrations of PSA, reduced slope of PSA doubling time, increased PSA doubling time, reduced metastasis as measured by bone scan, increased time to progression, increased survival time as compared to the Halabi nomogram, decreased serum concentrations of ICTP, or decreased concentrations of serum C-reactive protein.
28. The method of claim 15 , wherein the immune response is a humoral immune response.
29. A method for determining whether a subject is responding to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising administering an effective amount of a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, and detecting an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin, wherein detecting the immune response indicates that the subject is responding to said prostate cancer therapy.
30. The method of claim 29 , wherein the subject is a mammal.
31. The method of claim 29 , wherein the subject is a human.
32. The method of claim 29 , wherein the cancer cells are autologous.
33. The method of claim 29 , wherein the cancer cells are allogeneic.
34. The method of claim 29 , wherein the cancer cells are LnCaP cells or PC3 cells.
35. The method of claim 29 , further comprising detecting an immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9, wherein detecting the immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9 indicates that the subject is responding to said prostate cancer therapy.
36. The method of claim 29 , wherein an immune response is detected against HLA-A24.
37. The method of claim 29 , wherein an immune response is detected against OTUB2.
38. The method of claim 29 , wherein an immune response is detected against FLJ14668.
39. The method of claim 29 , wherein an immune response is detected against NNAT.
40. The method of claim 29 , wherein an immune response is detected against cardiolipin.
41. The method of claim 29 , wherein responsiveness to the cancer therapy is measured by decreased serum concentrations of tumor specific markers, increased overall survival time, increased progression-free survival, decreased tumor size, decreased bone metastasis marker response, increased impact on minimal residual disease, increased induction of antibody response to the cancer cells that have been rendered proliferation-incompetent, increased induction of delayed-type-hypersensitivity (DTH) response to injections of autologous tumor, increased induction of T cell response to autologous tumor or candidate tumor-associated antigens, increased impact on circulating T cell and dendritic cell numbers, phenotype, and function, cytokine response, decreased concentrations of PSA, reduced slope of PSA doubling time, increased PSA doubling time, reduced metastasis as measured by bone scan, increased time to progression, increased survival time as compared to the Halabi nomogram, decreased serum concentrations of ICTP, or decreased concentrations of serum C-reactive protein.
42. The method of claim 29 , wherein the immune response is a humoral immune response.
43. A computer-implemented method for determining whether a subject is responding to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising administering an effective amount of a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, inputting into a computer memory data indicating whether an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin is detected, inputting into the computer memory a correlation between an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin and responsiveness to said therapy, and determining whether the subject is responding to said therapy.
44. The method of claim 43 , wherein the subject is a mammal.
45. The method of claim 43 , wherein the subject is a human.
46. The method of claim 43 , wherein the cancer cells are autologous.
47. The method of claim 43 , wherein the cancer cells are allogeneic.
48. The method of claim 43 , wherein the cancer cells are LnCaP cells or PC3 cells.
49. The method of claim 43 , further comprising detecting an immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9, wherein detecting the immune response against an antigen listed in Table 1, 2, 3, 4, 5, 6, 7, or 9 indicates that the subject is responding to said prostate cancer therapy.
50. The method of claim 43 , wherein an immune response is detected against HLA-A24.
51. The method of claim 43 , wherein an immune response is detected against OTUB2.
52. The method of claim 43 , wherein an immune response is detected against FLJ14668.
53. The method of claim 43 , wherein an immune response is detected against NNAT.
54. The method of claim 43 , wherein an immune response is detected against cardiolipin.
55. The method of claim 43 , wherein responsiveness to the cancer therapy is measured by decreased serum concentrations of tumor specific markers, increased overall survival time, increased progression-free survival, decreased tumor size, decreased bone metastasis marker response, increased impact on minimal residual disease, increased induction of antibody response to the cancer cells that have been rendered proliferation-incompetent, increased induction of delayed-type-hypersensitivity (DTH) response to injections of autologous tumor, increased induction of T cell response to autologous tumor or candidate tumor-associated antigens, increased impact on circulating T cell and dendritic cell numbers, phenotype, and function, cytokine response, decreased concentrations of PSA, reduced slope of PSA doubling time, increased PSA doubling time, reduced metastasis as measured by bone scan, increased time to progression, increased survival time as compared to the Halabi nomogram, decreased serum concentrations of ICTP, or decreased concentrations of serum C-reactive protein.
56. A method for determining whether a subject is responding to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising detecting an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin, administering an effective amount of a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, and detecting an immune response against the antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin at a later second time, wherein an increase in the immune response detected at the later second time relative to the earlier first time indicates that the subject is responding to said prostate cancer therapy.
57. A computer-implemented method for determining whether a subject is responding to a prostate cancer therapy with a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-CSF, comprising administering an effective amount of a composition comprising cancer cells that have been rendered proliferation-incompetent and have been genetically engineered to express GM-C SF, inputting into a computer memory data indicating whether an immune response against an antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin is detected at a first time prior to said step of administering and at a later second time subsequent to said step of administering, inputting into the computer memory a correlation between an increase in the immune response against the antigen selected from the group consisting of HLA-A24, OTUB2, FLJ14668, NNAT, and cardiolipin at said later second time relative to said earlier first time and responsiveness to said therapy, and determining whether the subject is responding to said therapy.