JPWO2020102558A5 - - Google Patents

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JPWO2020102558A5
JPWO2020102558A5 JP2021526345A JP2021526345A JPWO2020102558A5 JP WO2020102558 A5 JPWO2020102558 A5 JP WO2020102558A5 JP 2021526345 A JP2021526345 A JP 2021526345A JP 2021526345 A JP2021526345 A JP 2021526345A JP WO2020102558 A5 JPWO2020102558 A5 JP WO2020102558A5
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cancer
compound
cell
foxp3
wing segment
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Priority claimed from PCT/US2019/061508 external-priority patent/WO2020102558A1/en
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８～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも８個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 8-80 linked nucleosides in length and that includes at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOS:9-3246. ９～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも９個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 9-80 linked nucleosides in length and that includes at least 9 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １０～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１０個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 10-80 bound nucleosides in length and that includes at least 10 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １１～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１１個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 11-80 linked nucleosides in length and that includes at least 11 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １２～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１２個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 12-80 linked nucleosides in length and that includes at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOS:9-3246. １６～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６のいずれか１つの核酸塩基配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide that is 16-80 linked nucleosides in length and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOS:9-3246. 配列番号９～３２４６のいずれか１つからなる核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence consisting of any one of SEQ ID NOS:9-3246. ８～８０個の結合ヌクレオシド長であり、且つ配列番号１のヌクレオチド２２６９～２２８４内に、又は配列番号２のヌクレオチド１２３３～１２４８、２１５６～２１７１、２７３５～２７５０、４６６１～４６７６、７３０７～７３２２、７３３１～７３４６、７９８０～７９９５、１１５８１～１１５９６、若しくは１２３９６～１２４１１内に相補的な修飾オリゴヌクレオチドを含む化合物。 8-80 linked nucleosides long and within nucleotides 2269-2284 of SEQ ID NO:1 or nucleotides 1233-1248, 2156-2171, 2735-2750, 4661-4676, 7307-7322, 7331 of SEQ ID NO:2 A compound comprising complementary modified oligonucleotides within -7346, 7980-7995, 11581-11596, or 12396-12411. 配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つを含む核酸塩基配列を有する、８～８０個の結合ヌクレオシド長である修飾オリゴヌクレオチドを含む化合物。 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575, comprising a modified oligonucleotide that is 8-80 linked nucleosides long and has a nucleobase sequence comprising any one of SEQ ID NOs: Compound. 配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つからなる核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence consisting of any one of SEQ ID NOs: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575. 前記修飾オリゴヌクレオチドは、少なくとも１つの修飾ヌクレオシド間結合、少なくとも１つの修飾糖、又は少なくとも１つの修飾核酸塩基を含む、請求項１～１０のいずれか一項に記載の化合物。 11. The compound of any one of claims 1-10, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar, or at least one modified nucleobase. 前記修飾ヌクレオシド間結合は、ホスホロチオアートヌクレオシド間結合である、請求項１１に記載の化合物。 12. The compound of Claim 11, wherein said modified internucleoside linkage is a phosphorothioate internucleoside linkage. 前記修飾糖は、二環式糖である、請求項１１又は１２に記載の化合物。 13. A compound according to claim 11 or 12, wherein said modified sugar is a bicyclic sugar. 前記二環式糖は：４’－（ＣＨ２）－Ｏ－２’（ＬＮＡ）；４’－（ＣＨ２）２－Ｏ－２’（ＥＮＡ）；及び４’－ＣＨ（ＣＨ３）－Ｏ－２’（ｃＥｔ）からなる群から選択される、請求項１３に記載の化合物。 The bicyclic sugars are: 4'-(CH 2 )-O-2'(LNA);4'-(CH 2 ) 2 -O-2'(ENA); and 4'-CH(CH 3 )- 14. The compound of claim 13, selected from the group consisting of O-2'(cEt). 前記修飾糖は、２’－Ｏ－メトキシエチルである、請求項１１又は１２に記載の化合物。 13. The compound of claim 11 or 12, wherein said modified sugar is 2'-O-methoxyethyl. 前記修飾核酸塩基は、５－メチルシトシンである、請求項１１～１５のいずれか一項に記載の化合物。 The compound of any one of claims 11-15, wherein said modified nucleobase is 5-methylcytosine. 前記修飾オリゴヌクレオチドは：
結合デオキシヌクレオシドからなるギャップセグメントと；
結合ヌクレオシドからなる５’ウイングセグメントと；
結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、修飾糖を含む、請求項１～１６のいずれか一項に記載の化合物。 Said modified oligonucleotide:
a gap segment consisting of linked deoxynucleosides;
a 5' wing segment consisting of linked nucleosides;
a 3' wing segment consisting of linked nucleosides;
17. The compound of any one of claims 1-16, wherein the gap segment is located between the 5' wing segment and the 3' wing segment, and each nucleoside of each wing segment comprises a modified sugar. . １６～８０個の結合ヌクレオシド長であり、且つ配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つを含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
結合デオキシヌクレオシドからなるギャップセグメントと；
結合ヌクレオシドからなる５’ウイングセグメントと；
結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、修飾糖を含む、化合物。 modified oligonucleotides that are 16-80 linked nucleosides long and have a nucleobase sequence that comprises any one of SEQ ID NOs: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575 A compound comprising the modified oligonucleotide:
a gap segment consisting of linked deoxynucleosides;
a 5' wing segment consisting of linked nucleosides;
a 3' wing segment consisting of linked nucleosides;
The compound, wherein the gap segment is located between the 5' wing segment and the 3' wing segment, and each nucleoside of each wing segment comprises a modified sugar. １６～８０個の結合核酸塩基長であり、且つ配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つに列挙される配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
１０個の結合デオキシヌクレオシドからなるギャップセグメントと；
３個の結合ヌクレオシドからなる５’ウイングセグメントと；
３個の結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、ｃＥｔヌクレオシドを含み、各ヌクレオシド間結合は、ホスホロチオアート結合であり、各シトシンは、５－メチルシトシンである、化合物。 A nucleobase sequence that is 16-80 bound nucleobases in length and comprises a sequence recited in any one of SEQ ID NOS: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575 A compound comprising a modified oligonucleotide having:
a gap segment consisting of 10 linked deoxynucleosides;
a 5' wing segment consisting of three linked nucleosides;
a 3' wing segment consisting of three linked nucleosides;
said gap segment is located between said 5′ wing segment and said 3′ wing segment, each nucleoside of each wing segment comprising a cEt nucleoside, each internucleoside linkage being a phosphorothioate linkage; A compound wherein each cytosine is 5-methylcytosine. １６～８０個の結合核酸塩基長であり、且つ配列番号４４９に列挙される配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
１０個の結合デオキシヌクレオシドからなるギャップセグメントと；
３個の結合ヌクレオシドからなる５’ウイングセグメントと；
３個の結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、ｃＥｔヌクレオシドを含み、各ヌクレオシド間結合は、ホスホロチオアート結合であり、各シトシンは、５－メチルシトシンである、化合物。 A compound comprising a modified oligonucleotide that is between 16 and 80 bound nucleobases in length and has a nucleobase sequence comprising the sequence recited in SEQ ID NO: 449, wherein said modified oligonucleotide:
a gap segment consisting of 10 linked deoxynucleosides;
a 5' wing segment consisting of three linked nucleosides;
a 3' wing segment consisting of three linked nucleosides;
said gap segment is located between said 5′ wing segment and said 3′ wing segment, each nucleoside of each wing segment comprising a cEt nucleoside, each internucleoside linkage being a phosphorothioate linkage; A compound wherein each cytosine is 5-methylcytosine. 前記オリゴヌクレオチドは、配列番号１～５のいずれかに少なくとも８０％、８５％、９０％、９５％、又は１００％相補的である、請求項１～２０のいずれか一項に記載の化合物。 21. The compound of any one of claims 1-20, wherein said oligonucleotide is at least 80%, 85%, 90%, 95%, or 100% complementary to any of SEQ ID NOs: 1-5. 一本鎖である、請求項１～２１のいずれか一項に記載の化合物。 The compound of any one of claims 1-21, which is single-stranded. 二本鎖である、請求項１～２１のいずれか一項に記載の化合物。 The compound of any one of claims 1-21, which is double-stranded. リボヌクレオチドを含む、請求項１～２３のいずれか一項に記載の化合物。 24. The compound of any one of claims 1-23, comprising a ribonucleotide. デオキシリボヌクレオチドを含む、請求項１～２３のいずれか一項に記載の化合物。 24. The compound of any one of claims 1-23, comprising deoxyribonucleotides. 前記修飾オリゴヌクレオチドは、１６～３０個の結合ヌクレオシドからなる、請求項１～２５のいずれか一項に記載の化合物。 The compound of any one of claims 1-25, wherein said modified oligonucleotide consists of 16-30 linked nucleosides. 前記修飾オリゴヌクレオチドからなる、請求項１～２６のいずれか一項に記載の化合物。 27. The compound of any one of claims 1-26, which consists of said modified oligonucleotide. 請求項１～２７のいずれか一項に記載の化合物の薬学的に許容され得る塩からなる化合物。 A compound consisting of a pharmaceutically acceptable salt of a compound according to any one of claims 1-27. 前記薬学的に許容され得る塩は、ナトリウム塩である、請求項２８に記載の化合物。 29. The compound of Claim 28, wherein said pharmaceutically acceptable salt is the sodium salt. 前記薬学的に許容され得る塩は、カリウム塩である、請求項２８に記載の化合物。 29. The compound of Claim 28, wherein said pharmaceutically acceptable salt is the potassium salt. 式：
Figure 2020102558000001
 又はその塩を有する化合物。 formula:
Figure 2020102558000001
 or a compound having a salt thereof. 式：
Figure 2020102558000002
 を有する化合物。 formula:
Figure 2020102558000002
 A compound having 請求項１～３２のいずれか一項に記載の化合物、及び薬学的に許容され得る担体を含む組成物。 33. A composition comprising a compound according to any one of claims 1-32 and a pharmaceutically acceptable carrier. 治療に用いられる、請求項１～３３のいずれか一項に記載の化合物又は修飾オリゴヌクレオチドを含む組成物。 34. A composition comprising the compound or modified oligonucleotide of any one of claims 1-33 for use in therapy. 個体において癌を治療し、又は寛解させるための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む、医薬組成物。 A pharmaceutical composition for treating or ameliorating cancer in an individual, the pharmaceutical composition comprising a compound that targets FOXP3. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項３５に記載の医薬組成物。 36. The pharmaceutical composition of claim 35, wherein said compound is an antisense compound targeting FOXP3. 前記癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項３５又は３６に記載の医薬組成物。 Said cancer is a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). Pharmaceutical composition as described. 前記医薬組成物を投与することで、免疫抑制、Ｔｒｅｇ免疫抑制活性、癌細胞増殖、腫瘍増殖、又は転移が阻害され、又は引き下げられ、或いは抗癌若しくは抗腫瘍免疫；抗癌若しくは抗腫瘍免疫応答；免疫細胞の活性化若しくは浸潤；炎症細胞の活性化若しくは浸潤；エフェクタ免疫細胞の活性化若しくは浸潤；Ｔ細胞の活性化若しくは浸潤；ＣＤ８ Ｔ細胞の活性化若しくは浸潤；ＮＫ細胞の活性化若しくは浸潤；マクロファージ及び樹状細胞の活性化若しくは浸潤；炎症；又は炎症性サイトカイン若しくはケモカインの発現が誘導され、又は活性化される、請求項３５～３７のいずれか一項に記載の医薬組成物。 Administration of said pharmaceutical composition inhibits or reduces immunosuppression, Treg immunosuppressive activity, cancer cell proliferation, tumor growth, or metastasis, or anti-cancer or anti-tumor immunity; activation or infiltration of immune cells; activation or infiltration of inflammatory cells; activation or infiltration of effector immune cells; activation or infiltration of T cells; activation or infiltration of CD8 T cells; activation or infiltration of macrophages and dendritic cells; inflammation; or expression of inflammatory cytokines or chemokines is induced or activated. 細胞におけるＦＯＸＰ３の発現を阻害する方法であって、前記細胞を、ＦＯＸＰ３を標的とする化合物と接触させることによって、前記細胞におけるＦＯＸＰ３の発現を阻害することを含む方法。 A method of inhibiting expression of FOXP3 in a cell, comprising inhibiting expression of FOXP3 in said cell by contacting said cell with a compound that targets FOXP3. 前記細胞は癌細胞である、請求項３９に記載の方法。 40. The method of claim 39, wherein said cells are cancer cells. 癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項４０に記載の方法。 Cancers are cancers with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or draining lymph node tumors, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) , head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small bowel cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophageal cancer , pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid, and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer, 41. The method of claim 40, which is myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). . 癌を患っている個体において、免疫抑制、Ｔｒｅｇ免疫抑制活性、癌細胞増殖、腫瘍増殖、又は転移を引き下げる、又は阻害するための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む医薬組成物。 A pharmaceutical composition for reducing or inhibiting immunosuppression, Treg immunosuppressive activity, cancer cell proliferation, tumor growth, or metastasis in an individual suffering from cancer, said pharmaceutical composition comprising a compound targeting FOXP3 thing. 癌を患っている個体において、抗癌若しくは抗腫瘍免疫；抗癌若しくは抗腫瘍免疫応答；免疫細胞の活性化若しくは浸潤；炎症細胞の活性化若しくは浸潤；エフェクタ免疫細胞の活性化若しくは浸潤；Ｔ細胞の活性化若しくは浸潤；ＣＤ８ Ｔ細胞の活性化若しくは浸潤；ＮＫ細胞の活性化若しくは浸潤；マクロファージ及び樹状細胞の活性化若しくは浸潤；炎症；又は炎症性サイトカイン若しくはケモカインの発現を誘導又は活性化するための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む医薬組成物。 anti-cancer or anti-tumor immunity; anti-cancer or anti-tumor immune response; immune cell activation or infiltration; inflammatory cell activation or infiltration; effector immune cell activation or infiltration; activation or infiltration of CD8 T cells; activation or infiltration of NK cells; activation or infiltration of macrophages and dendritic cells; inflammation; or expression of inflammatory cytokines or chemokines. comprising a compound that targets FOXP3. 前記個体は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）を患っている、請求項４３に記載の医薬組成物。 The individual has a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). Pharmaceutical composition as described. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項３５～４４のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-44, wherein said compound is an antisense compound targeting FOXP3. 前記化合物は、請求項１～３４のいずれか一項に記載の化合物である、請求項３５～４５のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-45, wherein said compound is a compound according to any one of claims 1-34. 前記医薬組成物は、非経口的に投与される、請求項３５～４６のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-46, wherein said pharmaceutical composition is administered parenterally. 癌を治療する、又は寛解させる医薬の製造における、ＦＯＸＰ３を標的とする化合物の使用。 Use of a compound targeting FOXP3 in the manufacture of a medicament for treating or ameliorating cancer. 前記癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項４８に記載の使用。 Said cancer is a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). use. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項４８又は４９に記載の使用。 50. Use according to claim 48 or 49, wherein said compound is an antisense compound targeting FOXP3. 前記化合物は、請求項１～３２のいずれか一項に記載の化合物である、請求項４８～５０のいずれか一項に記載の使用。 Use according to any one of claims 48-50, wherein said compound is a compound according to any one of claims 1-32.
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