METHODS FOR TREATING NEOPLASIA
The invention provides methods of treating neoplasia, for example bladder cancer, by administering an IL-2 fusion protein and one or more therapeutic agents, where the IL-2 fusion protein does not necessarily have to target the neoplasia.
1 . A method of ameliorating cancer in a subject comprising:
administering an effective amount of an IL-2 fusion protein and one or more therapeutic agents to the subject in need thereof, thereby ameliorate the cancer.
2 . The method of claim 1 , wherein the IL-2 fusion protein does not specifically target or bind to the cancer.
3 . The method of claim 1 , wherein the IL-2 fusion protein comprises a T cell receptor (TCR) domain.
4 . The method of claim 3 , wherein the T cell receptor domain is a single chain T cell receptor.
5 . The method of claim 1 , wherein the one or more therapeutic agents are selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, azacitidin, AZD 8477, bendamustin, bevacizumab, bexarotene, bicalutamide, BMS184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, bortezomib, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide (SEQ ID NO: 11), cachectin, capecitabin, cemadotin, cetuximab, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, dasatinib, daunorubicin, dolastatin, dovitinib, doxorubicin (adriamycin), epirubicin, epothilone B, erlotinib, eribulin, etoposide, everolimus, 5-fluorouracil, finasteride, flutamide, gefitinib, gemcitabine, hydroxyurea and hydroxyureataxanes, ifosfamide, interferon alfa, imatinib, ipilimumab, irinotecan, largotaxel, lapatinib, lenalidomid, liarozole, lonafarnib, lonidamine, lomustine (CCNU), mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, 5-fluorouracil, nilutamide, onapristone, oxaliplatin, paclitaxel, panitumumab, pazopanib, pralatrexate, prednimustine, piritrexim, procarbazine, pyrazoloacridine, rituximab, RPR109881, romidepsin, sorafinib, stramustine phosphate, sunitinib, tamoxifen, tasonermin, taxol, temozolomide, topotecan, transtuzumab, tretinoin, trimetrexate, vemurafenib, vinblastine, vincristine, vindesine sulfate, vinflunine, and vorinostat.
6 . The method of claim 1 , wherein the one or more therapeutic agents are selected from the group consisting of gemcitabine and platinum-based compounds including cisplatin.
7 . The method of claim 1 , wherein the cancer is selected from the group consisting of bladder cancer, urothelial cancer of the urethra, ureter and renal pelvis, multiple myeloma, kidney cancer, breast cancer, colon cancer, head and neck cancer, lung cancer, prostate cancer, glioblastoma, osteosarcoma, liposarcoma, soft-tissue sarcoma, ovarian cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer and stomach cancer.
8 . The method of claim 1 , wherein the cancer is bladder or urothelial cancer.
9 . The method of claim 1 , wherein the cancer is chemo-resistant.
10 . The method of claim 1 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 7-14 days.
11 . The method of claim 1 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 3-5 days or are administered concurrently.
12 . The method of claim 1 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents is cisplatin.
13 . The method of claim 12 , wherein the one or more therapeutic agents is gemcitabine.
14 . The method of claim 1 , wherein the IL-2 fusion protein specifically targets the cancer cells.
15 . The method of claim 14 , wherein the IL-2 fusion protein specifically targets p53 peptide/HLA complexes on the surface of the cancer cells.
16 . A method of reducing tumor burden in a subject comprising:
administering an effective amount of an IL-2 fusion protein and a therapeutic agent to the subject in need thereof, thereby reducing the tumor volume.
17 . The method of claim 16 , wherein the IL-2 fusion protein does not specifically target or bind to the cancer.
18 . The method of claim 16 , wherein the IL-2 fusion protein comprises a T cell receptor (TCR) domain.
19 . The method of claim 18 , wherein the T cell receptor domain is a single chain T cell receptor.
20 . The method of claim 16 , wherein the one or more therapeutic agents are selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, azacitidin, AZD 8477, bendamustin, bevacizumab, bexarotene, bicalutamide, BMS184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, bortezomib, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide (SEQ ID NO: 11), cachectin, capecitabin, cemadotin, cetuximab, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, dasatinib, daunorubicin, dolastatin, dovitinib, doxorubicin (adriamycin), epirubicin, epothilone B, erlotinib, eribulin, etoposide, everolimus, 5-fluorouracil, finasteride, flutamide, gefitinib, gemcitabine, hydroxyurea and hydroxyureataxanes, ifosfamide, interferon alfa, imatinib, ipilimumab, irinotecan, largotaxel, lapatinib, lenalidomid, liarozole, lonafarnib, lonidamine, lomustine (CCNU), mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, 5-fluorouracil, nilutamide, onapristone, oxaliplatin, paclitaxel, panitumumab, pazopanib, pralatrexate, prednimustine, piritrexim, procarbazine, pyrazoloacridine, rituximab, RPR109881, romidepsin, sorafinib, stramustine phosphate, sunitinib, tamoxifen, tasonermin, taxol, temozolomide, topotecan, transtuzumab, tretinoin, trimetrexate, vemurafenib, vinblastine, vincristine, vindesine sulfate, vinflunine, and vorinostat.
21 . The method of claim 16 , wherein the one or more therapeutic agents are selected from the group consisting of gemcitabine and platinum-based compounds including cisplatin.
22 . The method of claim 16 , wherein the tumor burden is selected from the group consisting of bladder cancer, urothelial cancer of the urethra, ureter and renal pelvis, multiple myeloma, kidney cancer, breast cancer, colon cancer, head and neck cancer, lung cancer, prostate cancer, glioblastoma, osteosarcoma, liposarcoma, soft-tissue sarcoma, ovarian cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer and stomach cancer.
23 . The method of claim 16 , wherein the tumor burden is bladder or urothelial cancer.
24 . The method of claim 16 , wherein the tumor burden is chemo-resistant.
25 . The method of claim 16 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 7-14 days.
26 . The method of claim 16 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 3-5 days or are administered concurrently.
27 . The method of claim 16 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents are gemcitabine and cisplatin.
28 . The method of claim 27 , wherein the one or more therapeutic agents is gemcitabine.
29 . The method of claim 16 , wherein the IL-2 fusion protein specifically targets the cancer cells.
30 . The method of claim 29 , wherein the IL-2 fusion protein specifically targets p53 peptide/HLA complexes on the surface of the cancer cells.
31 . A method of treating chemo-resistant cancer in a subject comprising:
administering an effective amount of an IL-2 fusion protein and a therapeutic agent to the subject in need thereof, thereby treating the chemo-resistant cancer.
32 . The method of claim 31 , wherein the IL-2 fusion protein does not specifically target or bind to the cancer.
33 . The method of claim 31 , wherein the IL-2 fusion protein comprises a T cell receptor (TCR) domain.
34 . The method of claim 33 , wherein the T cell receptor domain is a single chain T cell receptor.
35 . The method of claim 31 , wherein the one or more therapeutic agents are selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, azacitidin, AZD 8477, bendamustin, bevacizumab, bexarotene, bicalutamide, BMS184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, bortezomib, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide (SEQ ID NO: 11), cachectin, capecitabin, cemadotin, cetuximab, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, dasatinib, daunorubicin, dolastatin, dovitinib, doxorubicin (adriamycin), epirubicin, epothilone B, erlotinib, eribulin, etoposide, everolimus, 5-fluorouracil, finasteride, flutamide, gefitinib, gemcitabine, hydroxyurea and hydroxyureataxanes, ifosfamide, interferon alfa, imatinib, ipilimumab, irinotecan, largotaxel, lapatinib, lenalidomid, liarozole, lonafarnib, lonidamine, lomustine (CCNU), mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, 5-fluorouracil, nilutamide, onapristone, oxaliplatin, paclitaxel, panitumumab, pazopanib, pralatrexate, prednimustine, piritrexim, procarbazine, pyrazoloacridine, rituximab, RPR109881, romidepsin, sorafinib, stramustine phosphate, sunitinib, tamoxifen, tasonermin, taxol, temozolomide, topotecan, transtuzumab, tretinoin, trimetrexate, vemurafenib, vinblastine, vincristine, vindesine sulfate, vinflunine, and vorinostat.
36 . The method of claim 31 , wherein the one or more therapeutic agents are selected from the group consisting of gemcitabine and platinum-based compounds including cisplatin.
37 . The method of claim 31 , wherein the cancer is selected from the group consisting of bladder cancer, urothelial cancer of the urethra, ureter and renal pelvis, multiple myeloma, kidney cancer, breast cancer, colon cancer, head and neck cancer, lung cancer, prostate cancer, glioblastoma, osteosarcoma, liposarcoma, soft-tissue sarcoma, ovarian cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer and stomach cancer.
38 . The method of claim 31 , wherein the cancer is bladder or urothelial cancer.
39 . The method of claim 31 , wherein the cancer is chemo-resistant.
40 . The method of claim 31 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 7-14 days.
41 . The method of claim 31 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 3-5 days or are administered concurrently.
42 . The method of claim 31 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents is cisplatin.
43 . The method of claim 42 , wherein the one or more therapeutic agents is gemcitabine.
44 . The method of claim 31 , wherein the IL-2 fusion protein specifically targets the cancer cells.
45 . The method of claim 44 , wherein the IL-2 fusion protein specifically targets p53 peptide/HLA complexes on the surface of the cancer cells.
46 . A method of inducing a durable immunological memory response against cancer in a subject comprising:
administering an effective amount of an IL-2 fusion protein and a therapeutic agent to the subject in need thereof, thereby inducing a durable immunological memory response against cancer.
47 . The method of claim 46 , wherein the IL-2 fusion protein does not specifically target or bind to the cancer.
48 . The method of claim 46 , wherein the IL-2 fusion protein comprises a T cell receptor (TCR) domain.
49 . The method of claim 48 , wherein the T cell receptor domain is a single chain T cell receptor.
50 . The method of claim 46 , wherein the one or more therapeutic agents are selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, azacitidin, AZD 8477, bendamustin, bevacizumab, bexarotene, bicalutamide, BMS184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, bortezomib, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide (SEQ ID NO: 11), cachectin, capecitabin, cemadotin, cetuximab, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, dasatinib, daunorubicin, dolastatin, dovitinib, doxorubicin (adriamycin), epirubicin, epothilone B, erlotinib, eribulin, etoposide, everolimus, 5-fluorouracil, finasteride, flutamide, gefitinib, gemcitabine, hydroxyurea and hydroxyureataxanes, ifosfamide, interferon alfa, imatinib, ipilimumab, irinotecan, largotaxel, lapatinib, lenalidomid, liarozole, lonafarnib, lonidamine, lomustine (CCNU), mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, 5-fluorouracil, nilutamide, onapristone, oxaliplatin, paclitaxel, panitumumab, pazopanib, pralatrexate, prednimustine, piritrexim, procarbazine, pyrazoloacridine, rituximab, RPR109881, romidepsin, sorafinib, stramustine phosphate, sunitinib, tamoxifen, tasonermin, taxol, temozolomide, topotecan, transtuzumab, tretinoin, trimetrexate, vemurafenib, vinblastine, vincristine, vindesine sulfate, vinflunine, and vorinostat.
51 . The method of claim 46 , wherein the one or more therapeutic agents are selected from the group consisting of gemcitabine and platinum-based compounds including cisplatin.
52 . The method of claim 46 , wherein the cancer is selected from the group consisting of bladder cancer, urothelial cancer of the urethra, ureter and renal pelvis, multiple myeloma, kidney cancer, breast cancer, colon cancer, head and neck cancer, lung cancer, prostate cancer, glioblastoma, osteosarcoma, liposarcoma, soft-tissue sarcoma, ovarian cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer and stomach cancer.
53 . The method of claim 46 , wherein the cancer is bladder or urothelial cancer.
54 . The method of claim 46 , wherein the cancer is chemo-resistant.
55 . The method of claim 46 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 7-14 days.
56 . The method of claim 46 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 3-5 days or are administered concurrently.
57 . The method of claim 46 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents is cisplatin.
58 . The method of claim 57 , wherein the one or more therapeutic agents is gemcitabine.
59 . The method of claim 46 , wherein the IL-2 fusion protein specifically targets the cancer cells.
60 . The method of claim 59 , wherein the IL-2 fusion protein specifically targets p53 peptide/HLA complexes on the surface of the cancer cells.
61 . A method of increasing the survival of a subject having cancer comprising:
administering an effective amount of an IL-2 fusion protein and a therapeutic agent to the subject in need thereof, thereby increasing the survival of the subject.
62 . The method of claim 61 , wherein the IL-2 fusion protein does not specifically target or bind to the cancer.
63 . The method of claim 61 , wherein the IL-2 fusion protein comprises a T cell receptor (TCR) domain.
64 . The method of claim 63 , wherein the T cell receptor domain is a single chain T cell receptor.
65 . The method of claim 61 , wherein the one or more therapeutic agents are selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, azacitidin, AZD 8477, bendamustin, bevacizumab, bexarotene, bicalutamide, BMS184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, bortezomib, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide (SEQ ID NO: 11), cachectin, capecitabin, cemadotin, cetuximab, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, dasatinib, daunorubicin, dolastatin, dovitinib, doxorubicin (adriamycin), epirubicin, epothilone B, erlotinib, eribulin, etoposide, everolimus, 5-fluorouracil, finasteride, flutamide, gefitinib, gemcitabine, hydroxyurea and hydroxyureataxanes, ifosfamide, interferon alfa, imatinib, ipilimumab, irinotecan, largotaxel, lapatinib, lenalidomid, liarozole, lonafarnib, lonidamine, lomustine (CCNU), mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, 5-fluorouracil, nilutamide, onapristone, oxaliplatin, paclitaxel, panitumumab, pazopanib, pralatrexate, prednimustine, piritrexim, procarbazine, pyrazoloacridine, rituximab, RPR109881, romidepsin, sorafinib, stramustine phosphate, sunitinib, tamoxifen, tasonermin, taxol, temozolomide, topotecan, transtuzumab, tretinoin, trimetrexate, vemurafenib, vinblastine, vincristine, vindesine sulfate, vinflunine, and vorinostat.
66 . The method of claim 61 , wherein the one or more therapeutic agents are selected from the group consisting of gemcitabine and platinum-based compounds including cisplatin.
67 . The method of claim 61 , wherein the cancer is selected from the group consisting of bladder cancer, urothelial cancer of the urethra, ureter and renal pelvis, multiple myeloma, kidney cancer, breast cancer, colon cancer, head and neck cancer, lung cancer, prostate cancer, glioblastoma, osteosarcoma, liposarcoma, soft-tissue sarcoma, ovarian cancer, melanoma, liver cancer, esophageal cancer, pancreatic cancer and stomach cancer.
68 . The method of claim 61 , wherein the cancer is bladder or urothelial cancer.
69 . The method of claim 61 , wherein the cancer is chemo-resistant.
70 . The method of claim 61 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 7-14 days.
71 . The method of claim 61 , wherein the IL-2 fusion protein and the one or more therapeutic agents are administered within about 3-5 days or are administered concurrently.
72 . The method of claim 61 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents is cisplatin.
73 . The method of claim 72 , wherein the one or more therapeutic agents is gemcitabine.
74 . The method of claim 61 , wherein the IL-2 fusion protein specifically targets the cancer cells.
75 . The method of claim 74 , wherein the IL-2 fusion protein specifically targets p53 peptide/HLA complexes on the surface of the cancer cells.
76 . A kit for the treatment of bladder cancer comprising an IL-2 fusion protein and one or more therapeutic agents.
77 . The kit of claim 76 , wherein the IL-2 fusion protein is ALT-801 and the one or more therapeutic agents is cisplatin.
78 . The kit of claim 77 , wherein the one or more therapeutic agents is gemcitabine.