JPWO2021183873A5 - - Google Patents
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- JPWO2021183873A5 JPWO2021183873A5 JP2022554769A JP2022554769A JPWO2021183873A5 JP WO2021183873 A5 JPWO2021183873 A5 JP WO2021183873A5 JP 2022554769 A JP2022554769 A JP 2022554769A JP 2022554769 A JP2022554769 A JP 2022554769A JP WO2021183873 A5 JPWO2021183873 A5 JP WO2021183873A5
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- Prior art keywords
- cancer
- thio
- pharmaceutical composition
- inhibitor
- immune checkpoint
- Prior art date
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- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims 33
- 239000008194 pharmaceutical composition Substances 0.000 claims 33
- 206010028980 Neoplasm Diseases 0.000 claims 23
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims 22
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims 22
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims 20
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims 20
- 206010009944 Colon cancer Diseases 0.000 claims 14
- 201000011510 cancer Diseases 0.000 claims 13
- 238000000034 method Methods 0.000 claims 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 8
- 201000007270 liver cancer Diseases 0.000 claims 8
- 208000014018 liver neoplasm Diseases 0.000 claims 8
- 201000005202 lung cancer Diseases 0.000 claims 8
- 208000020816 lung neoplasm Diseases 0.000 claims 8
- 206010005003 Bladder cancer Diseases 0.000 claims 7
- 208000003174 Brain Neoplasms Diseases 0.000 claims 7
- 206010006187 Breast cancer Diseases 0.000 claims 7
- 208000026310 Breast neoplasm Diseases 0.000 claims 7
- 206010008342 Cervix carcinoma Diseases 0.000 claims 7
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 7
- 206010025323 Lymphomas Diseases 0.000 claims 7
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims 7
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims 7
- 206010033128 Ovarian cancer Diseases 0.000 claims 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 7
- 239000012270 PD-1 inhibitor Substances 0.000 claims 7
- 239000012668 PD-1-inhibitor Substances 0.000 claims 7
- 239000012271 PD-L1 inhibitor Substances 0.000 claims 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 7
- 206010060862 Prostate cancer Diseases 0.000 claims 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 7
- 208000000453 Skin Neoplasms Diseases 0.000 claims 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 7
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 7
- 206010057644 Testis cancer Diseases 0.000 claims 7
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 7
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 7
- 201000010881 cervical cancer Diseases 0.000 claims 7
- 208000029742 colonic neoplasm Diseases 0.000 claims 7
- 206010017758 gastric cancer Diseases 0.000 claims 7
- 201000010536 head and neck cancer Diseases 0.000 claims 7
- 208000014829 head and neck neoplasm Diseases 0.000 claims 7
- 208000032839 leukemia Diseases 0.000 claims 7
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 7
- 201000005443 oral cavity cancer Diseases 0.000 claims 7
- 201000002528 pancreatic cancer Diseases 0.000 claims 7
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 7
- 229940121655 pd-1 inhibitor Drugs 0.000 claims 7
- 229940121656 pd-l1 inhibitor Drugs 0.000 claims 7
- 201000000849 skin cancer Diseases 0.000 claims 7
- 201000011549 stomach cancer Diseases 0.000 claims 7
- 201000003120 testicular cancer Diseases 0.000 claims 7
- 201000005112 urinary bladder cancer Diseases 0.000 claims 7
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 6
- 208000002030 Merkel cell carcinoma Diseases 0.000 claims 6
- 206010027406 Mesothelioma Diseases 0.000 claims 6
- 208000034578 Multiple myelomas Diseases 0.000 claims 6
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 6
- 206010029260 Neuroblastoma Diseases 0.000 claims 6
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 claims 6
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 6
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 6
- 206010038389 Renal cancer Diseases 0.000 claims 6
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 6
- 201000009036 biliary tract cancer Diseases 0.000 claims 6
- 208000020790 biliary tract neoplasm Diseases 0.000 claims 6
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 claims 6
- 201000004101 esophageal cancer Diseases 0.000 claims 6
- 201000010982 kidney cancer Diseases 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- 206010028537 myelofibrosis Diseases 0.000 claims 6
- 238000001959 radiotherapy Methods 0.000 claims 6
- 206010038038 rectal cancer Diseases 0.000 claims 6
- 201000001275 rectum cancer Diseases 0.000 claims 6
- 238000002560 therapeutic procedure Methods 0.000 claims 6
- 206010046766 uterine cancer Diseases 0.000 claims 6
- 239000012275 CTLA-4 inhibitor Substances 0.000 claims 5
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 5
- 229940121420 cemiplimab Drugs 0.000 claims 5
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 229960003852 atezolizumab Drugs 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- -1 hormonal therapy Substances 0.000 claims 2
- 238000001794 hormone therapy Methods 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 229960003301 nivolumab Drugs 0.000 claims 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 claims 2
- 229940121497 sintilimab Drugs 0.000 claims 2
- 229950007213 spartalizumab Drugs 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 239000003053 toxin Substances 0.000 claims 2
- 231100000765 toxin Toxicity 0.000 claims 2
- 229940125568 MGD013 Drugs 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 229950002916 avelumab Drugs 0.000 claims 1
- 229940121418 budigalimab Drugs 0.000 claims 1
- 229950007712 camrelizumab Drugs 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 229940011248 cosibelimab Drugs 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 229940121432 dostarlimab Drugs 0.000 claims 1
- 229950009791 durvalumab Drugs 0.000 claims 1
- 230000008029 eradication Effects 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 230000001394 metastastic effect Effects 0.000 claims 1
- 206010061289 metastatic neoplasm Diseases 0.000 claims 1
- 229960002621 pembrolizumab Drugs 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- 229940018073 sasanlimab Drugs 0.000 claims 1
- 229950007123 tislelizumab Drugs 0.000 claims 1
- 229940121514 toripalimab Drugs 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 229940052007 zimberelimab Drugs 0.000 claims 1
Claims (26)
ๅ่จๆนๆณใฏใ6-ใใช-dGใๅ่จๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใซใใๅฆ็ฝฎใ็ถใใๅทฅ็จใๅซใฟใ
ๅ่จใใใใ่ต่ใใใ่บใใใไธญ็ฎ่ ซใ่ใใใ้ฃ้ใใใ่่ใใใ่้ใใใ่่ฑใใใ้ ญ้ ธ้จใใใๅฃ่ ใใใ้ผปๅฝ้ ญใใใๆไฝ่ณใใใ็ต่ ธใใใ็ด่ ธใใใ็ต่ ธ็ด่ ธใใใๅ็ซ่ บใใใๅตๅทฃใใใๅญๅฎฎ้ ธใใใๅญๅฎฎใใใ็ฒพๅทฃใใใใชใณใ่ ซใ็ฝ่ก็ ใ็ฎ่ใใใไนณใใใ่ ่ใใใ็ฅ็ต่ฝ็ดฐ่่ ซใใกใซใฑใซ็ดฐ่็ใ้ชจ้ซ็ฐๅฝขๆ็ๅ็พคใ้ชจ้ซ็ท็ถญ็ใใใใณๅค็บๆง้ชจ้ซ่ ซใใใชใ็พคใใ้ธๆใใใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
The method comprises administering 6-thio-dG to the subject, followed by treatment with an immune checkpoint inhibitor;
The cancers include pancreatic cancer, lung cancer, mesothelioma, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, bladder cancer, head and neck cancer, oral cavity cancer, nasopharyngeal cancer, and adult brain cancer. Colon cancer, rectal cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, uterine cancer, testicular cancer, lymphoma, leukemia, skin cancer, breast cancer, kidney cancer, A pharmaceutical composition selected from the group consisting of neuroblastoma, Merkel cell carcinoma, myelodysplastic syndrome, myelofibrosis, and multiple myeloma.
ๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใPD-L1้ปๅฎณๅคใงใใใใ
ๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใCTLA-4้ปๅฎณๅคใงใใใใ
ๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใใ1ใคใพใใฏ่คๆฐใฎCTLA-4้ปๅฎณๅคใจ1ใคใพใใฏ่คๆฐใฎPD-1้ปๅฎณๅคใจใฎ็ตใฟๅใใใงใใใใใพใใฏ
ๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใใ1ใคใพใใฏ่คๆฐใฎCTLA-4้ปๅฎณๅคใจ1ใคใพใใฏ่คๆฐใฎPD-L1้ปๅฎณๅคใจใฎ็ตใฟๅใใใงใใใ
่ซๆฑ้ 1่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ whether the immune checkpoint inhibitor is a PD-1 inhibitor;
whether the immune checkpoint inhibitor is a PD-L1 inhibitor;
whether the immune checkpoint inhibitor is a CTLA-4 inhibitor;
the immune checkpoint inhibitor is a combination of one or more CTLA-4 inhibitors and one or more PD-1 inhibitors, or
the immune checkpoint inhibitor is a combination of one or more CTLA-4 inhibitors and one or more PD-L1 inhibitors,
The pharmaceutical composition according to claim 1.
ใใงใใฏใใคใณใ้ปๅฎณๅคใใๆฒป็ใตใคใฏใซใใใ็ด1ๆฅ้๏ฝ็ด3ๆฅ้ๆไธใใใใ
่ซๆฑ้ 1ใพใใฏ2่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ 6-thio-dG is administered for about 1 day to about 5 days per treatment cycle, and/or
the checkpoint inhibitor is administered for about 1 day to about 3 days per treatment cycle;
The pharmaceutical composition according to claim 1 or 2 .
ๅ่จๆนๆณใใ6-ใใช-dGใๅ่จๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใใปใใใชใใ๏ผLibtayo๏ผ็ป้ฒๅๆจ๏ผ๏ผใซใใๅฆ็ฝฎใ็ถใใๅทฅ็จใๅซใฟใ
ๅ่จใใใใ่ต่ใใใ่บใใใไธญ็ฎ่ ซใ่ใใใ้ฃ้ใใใ่่ใใใ่้ใใใ่่ฑใใใ้ ญ้ ธ้จใใใๅฃ่ ใใใ้ผปๅฝ้ ญใใใๆไฝ่ณใใใ็ต่ ธใใใ็ด่ ธใใใ็ต่ ธ็ด่ ธใใใๅ็ซ่ บใใใๅตๅทฃใใใๅญๅฎฎ้ ธใใใๅญๅฎฎใใใ็ฒพๅทฃใใใใชใณใ่ ซใ็ฝ่ก็ ใ็ฎ่ใใใไนณใใใ่ ่ใใใ็ฅ็ต่ฝ็ดฐ่่ ซใใกใซใฑใซ็ดฐ่็ใ้ชจ้ซ็ฐๅฝขๆ็ๅ็พคใ้ชจ้ซ็ท็ถญ็ใใใใณๅค็บๆง้ชจ้ซ่ ซใใใชใ็พคใใ้ธๆใใใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
The method comprises administering 6-thio-dG to the subject, followed by treatment with cemiplimab (Libtayoยฎ);
The cancers include pancreatic cancer, lung cancer, mesothelioma, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, bladder cancer, head and neck cancer, oral cavity cancer, nasopharyngeal cancer, and adult brain cancer. Colon cancer, rectal cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, uterine cancer, testicular cancer, lymphoma, leukemia, skin cancer, breast cancer, kidney cancer, A pharmaceutical composition selected from the group consisting of neuroblastoma, Merkel cell carcinoma, myelodysplastic syndrome, myelofibrosis, and multiple myeloma.
ใปใใใชใใ๏ผLibtayo๏ผ็ป้ฒๅๆจ๏ผ๏ผใใๆฒป็ใตใคใฏใซใใใ็ด1ๆฅ้๏ฝ็ด3ๆฅ้ๆไธใใใใ
่ซๆฑ้ 5่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ 6-thio-dG is administered for about 1 day to about 5 days per treatment cycle, and/or
cemiplimab (Libtayoยฎ) is administered for about 1 to about 3 days per treatment cycle;
6. The pharmaceutical composition according to claim 5 .
ๅ่จๆนๆณใใ6-ใใช-dGใๅ่จๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใๆพๅฐ็ท็ๆณใจ็ตใฟๅใใใฆๆไธใใใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใซใใๅฆ็ฝฎใ็ถใใๅทฅ็จใๅซใฟใ
ๅ่จใใใใ่ต่ใใใ่บใใใไธญ็ฎ่ ซใ่ใใใ้ฃ้ใใใ่่ใใใ่้ใใใ่่ฑใใใ้ ญ้ ธ้จใใใๅฃ่ ใใใ้ผปๅฝ้ ญใใใๆไฝ่ณใใใ็ต่ ธใใใ็ด่ ธใใใ็ต่ ธ็ด่ ธใใใๅ็ซ่ บใใใๅตๅทฃใใใๅญๅฎฎ้ ธใใใๅญๅฎฎใใใ็ฒพๅทฃใใใใชใณใ่ ซใ็ฝ่ก็ ใ็ฎ่ใใใไนณใใใ่ ่ใใใ็ฅ็ต่ฝ็ดฐ่่ ซใใกใซใฑใซ็ดฐ่็ใ้ชจ้ซ็ฐๅฝขๆ็ๅ็พคใ้ชจ้ซ็ท็ถญ็ใใใใณๅค็บๆง้ชจ้ซ่ ซใใใชใ็พคใใ้ธๆใใใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
The method comprises administering 6-thio-dG to the subject, followed by treatment with an immune checkpoint inhibitor administered in combination with radiation therapy,
The cancers include pancreatic cancer, lung cancer, mesothelioma, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, bladder cancer, head and neck cancer, oral cavity cancer, nasopharyngeal cancer, and adult brain cancer. Colon cancer, rectal cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, uterine cancer, testicular cancer, lymphoma, leukemia, skin cancer, breast cancer, kidney cancer, A pharmaceutical composition selected from the group consisting of neuroblastoma, Merkel cell carcinoma, myelodysplastic syndrome, myelofibrosis, and multiple myeloma.
ๅ่จใใใ่ปข็งปๆงใงใใใ
ๅ่จใใใๅ็บๆงใงใใใใใใณ/ใพใใฏ
ๅ่จใใใๆฒป็ๆตๆๆงใงใใใ
่ซๆฑ้ 1๏ฝ9ใฎใใใใไธ้ ่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ the cancer is lung cancer, colorectal cancer, liver cancer, melanoma, or glioblastoma;
the cancer is metastatic;
said cancer is recurrent and/or
the cancer is resistant to treatment;
A pharmaceutical composition according to any one of claims 1 to 9 .
ๅ่จ6-ใใช-dGใใใณๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใ่ ซ็้จไฝใซๅฑๆ็ใซใพใใฏๅฑ้จ็ใซๆไธใใใใใใพใใฏ
ๅ่จ6-ใใช-dGใ่ ซ็้จไฝใซๅฑๆ็ใซใพใใฏๅฑ้จ็ใซๆไธใใใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใๅ จ่บซ็ใซๆไธใใใใ
่ซๆฑ้ 1๏ฝ15ใฎใใใใไธ้ ่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ said 6-thio-dG and immune checkpoint inhibitor are administered systemically;
said 6-thio-dG and immune checkpoint inhibitor are administered locally or regionally to the tumor site; or
the 6-thio-dG is administered locally or regionally to the tumor site, and the immune checkpoint inhibitor is administered systemically;
Pharmaceutical composition according to any one of claims 1 to 15 .
6-ใใช-dGใใใณๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใฎๆไธใๅ่จใใใฎๅฏ่งฃใใใใใใ
6-ใใช-dGใใใณๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใฎๆไธใ่ ซ็้ใฎไฝไธใใใใใใ
6-ใใช-dGใใใณๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใฎๆไธใใใ็ดฐ่่ปข็งปใฎ้ปๅฎณใใใใใใใใใณ/ใพใใฏ
6-ใใช-dGใใใณๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใฎๆไธใ่ ซ็ๆ น็ตถใใใใใใ
่ซๆฑ้ 1๏ฝ16ใฎใใใใไธ้ ่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ Administration of 6-thio-dG and immune checkpoint inhibitors results in inhibition of tumor growth,
administration of 6-thio-dG and an immune checkpoint inhibitor results in remission of said cancer;
Administration of 6-thio-dG and immune checkpoint inhibitors results in decreased tumor burden;
administration of 6-thio-dG and an immune checkpoint inhibitor results in inhibition of cancer cell metastasis, and/or
Administration of 6-thio-dG and immune checkpoint inhibitors results in tumor eradication,
A pharmaceutical composition according to any one of claims 1 to 16 .
ๅ่จๆนๆณใใ6-ใใช-dGใๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใๆพๅฐ็ท็ๆณใซใใๅฆ็ฝฎใ็ถใใๅทฅ็จใๅซใฟใ
ๅ่จใใใใ่ต่ใใใ่บใใใไธญ็ฎ่ ซใ่ใใใ้ฃ้ใใใ่่ใใใ่้ใใใ่่ฑใใใ้ ญ้ ธ้จใใใๅฃ่ ใใใ้ผปๅฝ้ ญใใใๆไฝ่ณใใใ็ต่ ธใใใ็ด่ ธใใใ็ต่ ธ็ด่ ธใใใๅ็ซ่ บใใใๅตๅทฃใใใๅญๅฎฎ้ ธใใใๅญๅฎฎใใใ็ฒพๅทฃใใใใชใณใ่ ซใ็ฝ่ก็ ใ็ฎ่ใใใไนณใใใ่ ่ใใใ็ฅ็ต่ฝ็ดฐ่่ ซใใกใซใฑใซ็ดฐ่็ใ้ชจ้ซ็ฐๅฝขๆ็ๅ็พคใ้ชจ้ซ็ท็ถญ็ใใใใณๅค็บๆง้ชจ้ซ่ ซใใใชใ็พคใใ้ธๆใใใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
The method comprises administering 6-thio-dG to a subject, followed by treatment with radiation therapy,
The cancers include pancreatic cancer, lung cancer, mesothelioma, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, bladder cancer, head and neck cancer, oral cavity cancer, nasopharyngeal cancer, and adult brain cancer. Colon cancer, rectal cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, uterine cancer, testicular cancer, lymphoma, leukemia, skin cancer, breast cancer, kidney cancer, A pharmaceutical composition selected from the group consisting of neuroblastoma, Merkel cell carcinoma, myelodysplastic syndrome, myelofibrosis, and multiple myeloma.
ๅ่จๆนๆณใใ6-ใใช-dGใๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใๆพๅฐ็ท็ๆณใซใใๅฆ็ฝฎใๅ ่กใใใๅทฅ็จใๅซใฟใ
ๅ่จใใใใ่ต่ใใใ่บใใใไธญ็ฎ่ ซใ่ใใใ้ฃ้ใใใ่่ใใใ่้ใใใ่่ฑใใใ้ ญ้ ธ้จใใใๅฃ่ ใใใ้ผปๅฝ้ ญใใใๆไฝ่ณใใใ็ต่ ธใใใ็ด่ ธใใใ็ต่ ธ็ด่ ธใใใๅ็ซ่ บใใใๅตๅทฃใใใๅญๅฎฎ้ ธใใใๅญๅฎฎใใใ็ฒพๅทฃใใใใชใณใ่ ซใ็ฝ่ก็ ใ็ฎ่ใใใไนณใใใ่ ่ใใใ็ฅ็ต่ฝ็ดฐ่่ ซใใกใซใฑใซ็ดฐ่็ใ้ชจ้ซ็ฐๅฝขๆ็ๅ็พคใ้ชจ้ซ็ท็ถญ็ใใใใณๅค็บๆง้ชจ้ซ่ ซใใใชใ็พคใใ้ธๆใใใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
The method comprises administering 6-thio-dG to a subject, which is preceded by treatment with radiation therapy;
The cancers include pancreatic cancer, lung cancer, mesothelioma, stomach cancer, esophageal cancer, liver cancer, biliary tract cancer, bladder cancer, head and neck cancer, oral cavity cancer, nasopharyngeal cancer, and adult brain cancer. Colon cancer, rectal cancer, colorectal cancer, prostate cancer, ovarian cancer, cervical cancer, uterine cancer, testicular cancer, lymphoma, leukemia, skin cancer, breast cancer, kidney cancer, A pharmaceutical composition selected from the group consisting of neuroblastoma, Merkel cell carcinoma, myelodysplastic syndrome, myelofibrosis, and multiple myeloma.
ๅ่จๆนๆณใใ6-ใใช-dGใๅฏพ่ฑกใซๆไธใใๅทฅ็จใงใใฃใฆใใใใซใๅ ็ซใใงใใฏใใคใณใ้ปๅฎณๅคใใใณๆพๅฐ็ท็ๆณใซใใๅฆ็ฝฎใ็ถใใๅทฅ็จใๅซใใ่ฌๅญฆ็็ตๆ็ฉใ A pharmaceutical composition for use in a method of treating cancer in a subject, comprising 6-thio-2'-deoxyguanosine (6-thio-dG), the composition comprising:
A pharmaceutical composition, wherein the method comprises administering 6-thio-dG to a subject, followed by treatment with an immune checkpoint inhibitor and radiation therapy.
PD-L1้ปๅฎณๅคใใขใใพใชใบใใใงใใใใใพใใฏ
PD-1้ปๅฎณๅคใใใใณใใญใชใบใใใใใใซใใใใปใใใชใใใJTx-4014ใใตใตใณใชใใใใใใฃใฌใชใใใBI754091ใในใใซใฟใชใบใใใใซใ ใฌใชใบใใใใทใณใใชใใใใในใฌใชใบใใใใธใณใใฌใชใใใใใชใใชใใใใในใฟใซใชใใใINCMGA00012ใAMP-224ใREGN2810ใBMS-936558ใSHR1210ใIBI308ใPDR001ใBGB-A317ใBCD-100ใJS001ใใใณAMP-515ใฎ1ใคใพใใฏ่คๆฐใใ้ธๆใใใใ
่ซๆฑ้ 23่จ่ผใฎ่ฌๅญฆ็็ตๆ็ฉใ the PD-L1 inhibitor is selected from one or more of atezolizumab, avelumab, cosibelimab, bintrafusupalfa, durvalumab, MGD013, KNO35, KN046, AUNP12, CA-170, and BMS-9986189;
the PD-L1 inhibitor is atezolizumab , or
PD-1 inhibitors include pembrolizumab, nivolumab, cemiplimab, JTx-4014, sasanlimab, budigalimab, BI754091, spartalizumab, camrelizumab, sintilimab, tislelizumab, zimberelimab, toripalimab, dostarlimab, INCMGA00012, AMP-224, REGN2810, BMS-936558 , SHR1210, IBI308, PDR001, BGB-A317, BCD-100, JS001 and AMP-515,
24. The pharmaceutical composition according to claim 23 .
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| US202062989041P | 2020-03-13 | 2020-03-13 | |
| US62/989,041 | 2020-03-13 | ||
| PCT/US2021/022090 WO2021183873A1 (en) | 2020-03-13 | 2021-03-12 | Sequential treatment of cancers using 6-thio-dg, checkpoint inhibitors and radiation therapy |
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| WO2012052181A1 (en) * | 2010-10-22 | 2012-04-26 | Roche Diagnostics Gmbh | A conjugate between a thiophilic solid phase and an oligonucleotide comprising a thiooxonucleotide |
| CA2991628C (en) * | 2015-07-16 | 2020-04-07 | Bioxcel Therapeutics, Inc. | A novel approach for treatment of cancer using immunomodulation |
| US20180036331A1 (en) * | 2016-03-24 | 2018-02-08 | The Board Of Regents Of The University Of Texas System | Treatment of drug resistant proliferative diseases with telomerase mediated telomere altering compounds |
| AU2017271615A1 (en) * | 2016-05-27 | 2018-12-20 | The Board Of Regents Of The University Of Texas System | 6-thio-2'-deoxyguanosine (6-thio-dG) results in telomerase dependent telomere dysfunction and cell death in therapy-resistant cancer cells |
| IL265274B2 (en) * | 2016-09-16 | 2023-11-01 | Bionomics Ltd | Combination of anti-lgr5 antibody and antibody inhibitor of pd-1 for tumour treatment |
| AU2018225102A1 (en) * | 2017-02-21 | 2019-09-05 | Regeneron Pharmaceuticals, Inc. | Anti-PD-1 antibodies for treatment of lung cancer |
| WO2019152574A1 (en) * | 2018-02-01 | 2019-08-08 | Merck Sharp & Dohme Corp. | Methods for treating cancer or infection using a combination of an anti-pd-1 antibody, an anti-lag3 antibody, and an anti-tigit antibody |
| US20210023107A1 (en) * | 2018-03-22 | 2021-01-28 | The Board Of Regents Of The University Of Texas System | USE OF 6-THIO-dG TO TREAT THERAPY-RESISTANT TELOMERASEPOSITIVE PEDIATRIC BRAIN TUMORS |
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