RU2018141200A - Способы и композиции для лечения опухолей - Google Patents
Способы и композиции для лечения опухолей Download PDFInfo
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- RU2018141200A RU2018141200A RU2018141200A RU2018141200A RU2018141200A RU 2018141200 A RU2018141200 A RU 2018141200A RU 2018141200 A RU2018141200 A RU 2018141200A RU 2018141200 A RU2018141200 A RU 2018141200A RU 2018141200 A RU2018141200 A RU 2018141200A
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- 238000000034 method Methods 0.000 title claims 8
- 239000000203 mixture Substances 0.000 title claims 5
- 206010028980 Neoplasm Diseases 0.000 title claims 4
- 210000004027 cell Anatomy 0.000 claims 26
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims 7
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims 7
- 239000003795 chemical substances by application Substances 0.000 claims 5
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical group CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims 4
- 239000000427 antigen Substances 0.000 claims 4
- 108091007433 antigens Proteins 0.000 claims 4
- 102000036639 antigens Human genes 0.000 claims 4
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims 4
- 230000000644 propagated effect Effects 0.000 claims 4
- 229960005486 vaccine Drugs 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 3
- 230000000735 allogeneic effect Effects 0.000 claims 2
- 210000000170 cell membrane Anatomy 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 210000001671 embryonic stem cell Anatomy 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 230000000415 inactivating effect Effects 0.000 claims 2
- 239000003471 mutagenic agent Substances 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 210000000130 stem cell Anatomy 0.000 claims 2
- 229960000604 valproic acid Drugs 0.000 claims 2
- MAUCONCHVWBMHK-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide Chemical compound O1C2=CC=CC=C2C(CN(C)C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 MAUCONCHVWBMHK-UHFFFAOYSA-N 0.000 claims 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 claims 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims 1
- 229940126190 DNA methyltransferase inhibitor Drugs 0.000 claims 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims 1
- YALNUENQHAQXEA-UHFFFAOYSA-N N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester Chemical compound C1=CC2=CC(CN(CC)CC)=CC=C2C=C1COC(=O)NC1=CC=C(C(=O)NO)C=C1 YALNUENQHAQXEA-UHFFFAOYSA-N 0.000 claims 1
- 229950008805 abexinostat Drugs 0.000 claims 1
- 229960002756 azacitidine Drugs 0.000 claims 1
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 claims 1
- 229960003094 belinostat Drugs 0.000 claims 1
- 229940022399 cancer vaccine Drugs 0.000 claims 1
- 238000009566 cancer vaccine Methods 0.000 claims 1
- 229950009221 chidamide Drugs 0.000 claims 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 claims 1
- 229950005837 entinostat Drugs 0.000 claims 1
- 229950010415 givinostat Drugs 0.000 claims 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims 1
- 231100000636 lethal dose Toxicity 0.000 claims 1
- 231100000350 mutagenesis Toxicity 0.000 claims 1
- 238000002703 mutagenesis Methods 0.000 claims 1
- WXHHICFWKXDFOW-BJMVGYQFSA-N n-(2-amino-5-fluorophenyl)-4-[[[(e)-3-pyridin-3-ylprop-2-enoyl]amino]methyl]benzamide Chemical compound NC1=CC=C(F)C=C1NC(=O)C(C=C1)=CC=C1CNC(=O)\C=C\C1=CC=CN=C1 WXHHICFWKXDFOW-BJMVGYQFSA-N 0.000 claims 1
- 229960005184 panobinostat Drugs 0.000 claims 1
- FWZRWHZDXBDTFK-ZHACJKMWSA-N panobinostat Chemical compound CC1=NC2=CC=C[CH]C2=C1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FWZRWHZDXBDTFK-ZHACJKMWSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 claims 1
- 229960000237 vorinostat Drugs 0.000 claims 1
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Claims (27)
1. Применение комбинации (I) ингибитора гистондезацетилазы (HDACi) и (II) композиции вакцины, содержащей популяцию плюрипотентных клеток, которые были инактивированы для получения лекарственного средства для одновременного, раздельного или последовательного введения для терапевтического или профилактического лечения рака у субъекта.
2. Применение по п. 1, где субъект представляет собой человека.
3. Применение по п. 1, дополнительно включающее HDACi для введения через некоторое время после введения композиции вакцины.
4. Применение по любому из пп. 1-3, где популяция плюрипотентных клеток была получена путем:
a) размножения плюрипотентных клеток при наличии таких условий, которые поддерживают плюрипотентную способность клеток, в присутствии агента, который индуцирует презентацию антигенов MHC-I (Главным комплексом гистосовместимости 1-го класса) у указанной популяции во время стадии размножения;
b) подвергания размноженных клеток воздействию инактивирующего агента, который инактивирует клетки, при этом сохраняя целостность клеточной оболочки;
c) восстановления и консервации размноженных инактивированных клеток.
5. Применение по любому из пп. 1-4, где клетки популяции экспрессируют представляющий интерес антиген, также экспрессируемый раковыми клетками субъекта, и, в частности, неоантиген.
6. Способ получения популяции плюрипотентных клеток, которые были инактивированы, включающий стадии:
I) размножения плюрипотентных клеток при наличии таких условий, которые поддерживают плюрипотентную способность клеток, в присутствии агента, который индуцирует презентацию антигенов MHC-I у указанной популяции во время стадии размножения;
II) подвергания размноженных клеток воздействию инактивирующего агента, который инактивирует клетки, при этом сохраняя целостность клеточной оболочки;
III) восстановления и консервации размноженных инактивированных клеток.
7. Способ по п. 6, где популяция плюрипотентных клеток выбрана из группы, состоящей из эмбриональных стволовых клеток человека, индуцированных плюрипотентных стволовых клеток (iPS), аллогенных, ксеногенных, аутологичных и сингенных стволовых клеток.
8. Способ по п. 6 или 7, где плюрипотентные клетки подвергают воздействию мутагенного агента во время размножения, с тем чтобы индуцировать мутагенез генов в клетках указанной популяции.
9. Способ по любому из пп. 6-8, где агент, который индуцирует презентацию антигенов MHC-I и усиливает плюрипотентный ген, представляет собой ингибитор гистондезацетилазы (HDACi).
10. Способ по п. 9, где ингибитор гистондезацетилазы выбран из группы, состоящей из вальпроевой кислоты (VPA), вориностата, панобиностата, гивиностата, белиностата, энтиностата, моцетиностата, практиностата, чидамида, квизиностата и абексиностата.
11. Способ по любому из пп. 6-10, где на стадии I) присутствует ингибитор ДНК-метилтрансферазы, в частности 5-азацитидин.
12. Способ по любому из пп. 6-11, где клетки инактивируют воздействием летальной дозы облучения.
13. Композиция противораковой вакцины вакцины, содержащая:
a) популяцию инактивированных плюрипотентных клеток и
b) ингибитор гистондезацетилазы.
14. Композиция вакцины по п. 13, где плюрипотентные клетки содержат мутагенезированные плюрипотентные клетки.
15. Применение комбинированного препарата из I) популяции инактивированных плюрипотентных клеток и II) соединения, которое активирует экспрессию МНС и/или иммунный ответ для получения лекарственного средства для одновременного, отдельного или последовательного введения для лечения субъекта, страдающего от рака.
16. Применение по п. 15, где популяция плюрипотентных клеток выбрана из группы, состоящей из эмбриональных стволовых клеток человека, индуцированных плюрипотентных стволовых клеток (iPS), аллогенных, ксеногенных, аутологичных или сингенных стволовых клеток.
17. Применение по п. 15 или 16, где плюрипотентные клетки генетически модифицированы для сверхэкспрессии соединений, которые стимулируют экспрессию МНС и/или иммунный ответ.
18. Применение по любому из пп. 15-17, где плюрипотентные клетки были обработаны мутагенным агентом.
19. Применение по любому из пп. 15-18, дополнительно включающее введение ингибитора иммунных контрольных точек субъекту.
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