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Description
他の実施形態
本発明をその詳細な説明と関連づけて説明したが、前述の説明は添付の特許請求の範囲によって定義される本発明の範囲を例示するものであり、限定するものではないことを理解されたい。他の態様、利点、および変更は、以下の特許請求の範囲内にある。
以下に、本願の当初の特許請求の範囲に記載の発明を列挙する。
［発明１］
外因性ＤＮＡ分子、外因性ＲＮＡ分子、外因性タンパク質、または外因性ペプチドのうちの少なくとも１つを発現するように遺伝子操作された除核細胞を含む治療有効量の組成物を対象に投与するステップを含む、対象における疾患を処置する方法。
［発明２］
前記組成物が、治療剤をさらに含む、発明１に記載の方法。
［発明３］
前記治療剤が、低分子ＲＮＡ、低分子薬、ペプチド、ウイルス、またはそれらの組合せのうちの少なくとも１つを含む、発明２に記載の方法。
［発明４］
前記治療剤が、化学療法剤を含む、発明２に記載の方法。
［発明５］
免疫系を活性化するように遺伝子操作されている除核細胞を対象に投与するステップを含む、対象における免疫活性化を制御する方法。
［発明６］
前記除核細胞が、少なくとも１つの外因性タンパク質を発現するように遺伝子操作されている、発明５に記載の方法。
［発明７］
前記外因性タンパク質が、細胞表面タンパク質である、発明６に記載の方法。
［発明８］
前記外因性タンパク質が、免疫活性化タンパク質である、発明７に記載の方法。
［発明９］
前記外因性タンパク質が、サイトカイン、ＩＬ－１２、カルレティキュリン、ホスファチジリシン、食作用プレイ結合ドメイン、アネキシン１、ＯＸ４０／ＯＣ４０Ｌ、４－１ＢＢ、Ｂ７ファミリーメンバー、またはそれらの組合せを含む、発明６から８のいずれか一つに記載の方法。
［発明１０］
免疫系による認識を回避するように遺伝子操作されている除核細胞を対象に投与するステップを含む、対象における免疫認識を制御する方法。
［発明１１］
前記除核細胞が、除核細胞から免疫認識分子を枯渇させるように遺伝子操作されている、発明１０に記載の方法。
［発明１２］
前記免疫認識分子が、ＨＬＡ抗原、プロテオグリカン、糖部分、胚抗原、またはそれらの組合せを含む、発明１１に記載の方法。
［発明１３］
前記除核細胞が、少なくとも１つの外因性タンパク質を発現するように遺伝子操作されている、発明１０に記載の方法。
［発明１４］
前記外因性タンパク質が、細胞表面タンパク質である、発明１３に記載の方法。
［発明１５］
前記外因性タンパク質が、免疫回避分子である、発明１３に記載の方法。
［発明１６］
前記外因性タンパク質が、サイトカイン、ＩＬ－１、ＩＬ－４、ＩＬ－６、ＩＬ－８、ＩＬ－１０、ＴＧＦ－β、ＩＧＦ－２、ＶＥＧＦ、ＴＮＦ－アルファ、ＣＤ４７、ＨＬＡ－Ｅ、ＨＬＡ－Ｇ、ＨＬＡ－Ｅ／Ｇ、ＰＤ－１、ＰＤ－Ｌ１、ＴＩＧＩＴ、ＣＤ１１２Ｒ、ＣＴＬＡ－４、ケモカイン、ケモカインリガンド１、Ｃ－Ｃモチーフケモカイン受容体７、ＮＫ阻害受容体、ＨＬＡ－クラスＩ特異的阻害性受容体、キラー細胞免疫グロブリン様受容体（ＫＩＲ）、ＮＫＧ２Ａ、リンパ球活性化遺伝子－３（ＬＡＧ－３）、またはそれらの組合せを含む、発明１５に記載の方法。
［発明１７］
外因性ＤＮＡ分子、外因性ＲＮＡ分子、外因性タンパク質、または外因性ペプチドのうちの少なくとも１つを発現するように遺伝子操作された除核細胞を対象に投与するステップを含み、
前記遺伝子操作された除核細胞が、疾患状態の存在または位置を識別する、対象における疾患状態の存在を識別する方法。
［発明１８］
前記外因性タンパク質が、炎症ホーミング受容体である、発明１７に記載の方法。
［発明１９］
前記炎症ホーミング受容体が、前記除核細胞を損傷組織および／または炎症組織に誘導する、発明１８に記載の方法。
［発明２０］
前記除核細胞が、ナチュラルキラー（ＮＫ）細胞、マクロファージ、好中球、線維芽細胞、および成体幹細胞、間葉系間質細胞（ＭＳＣ）、誘導多能性幹細胞、またはそれらの組合せに由来する、発明１から１９のいずれか一つに記載の方法。
［発明２１］
前記除核細胞が、間葉系間質細胞（ＭＳＣ）に由来する、発明２０に記載の方法。
［発明２２］
前記外因性ＤＮＡ分子が、一本鎖ＤＮＡ、二本鎖ＤＮＡ、オリゴヌクレオチド、プラスミド、細菌ＤＮＡ分子、ＤＮＡウイルス、またはそれらの組合せを含む、発明１から２１のいずれか一つに記載の方法。
［発明２３］
前記外因性ＲＮＡ分子が、メッセンジャーＲＮＡ（ｍＲＮＡ）、低分子干渉ＲＮＡ（ｓｉＲＮＡ）、マイクロＲＮＡ（ｍｉＲＮＡ）、ショートヘアピンＲＮＡ（ｓｈＲＮＡ）、ＲＮＡウイルス、またはそれらの組合せを含む、発明１から２２のいずれか一つに記載の方法。
［発明２４］
前記外因性タンパク質が、サイトカイン、増殖因子、ホルモン、抗体、酵素、またはそれらの組合せを含む、発明１から２３のいずれか一つに記載の方法。
［発明２５］
前記投与するステップが、静脈内投与、皮下投与、腹腔内投与、直腸投与、経口投与、またはそれらの組合せを含む、発明１から２４のいずれか一つに記載の方法。
［発明２６］
前記投与するステップが、腫瘍内投与を含む、発明２５に記載の方法。
［発明２７］
前記疾患が、炎症、感染、がん、神経疾患、自己免疫疾患、心血管疾患、眼科疾患、骨格疾患、代謝性疾患、またはそれらの組合せを含む、発明１から２６のいずれか一つに記載の方法。
［発明２８］
前記がんが、多発性骨髄腫、神経膠芽腫、リンパ腫、白血病、中皮腫、肉腫、乳がん、前立腺がん、卵巣がん、膵がん、結腸がん、またはそれらの組合せを含む、発明２７に記載の方法。
Other Embodiments Although the invention has been described in connection with the detailed description thereof, it is to be understood that the foregoing description is illustrative of the scope of the invention as defined by the appended claims, and is not intended to be limiting. I want to be understood. Other aspects, advantages, and modifications are within the scope of the following claims.
The inventions described in the original claims of this application are listed below.
[Invention 1]
administering to the subject a therapeutically effective amount of a composition comprising enucleated cells genetically engineered to express at least one of an exogenous DNA molecule, an exogenous RNA molecule, an exogenous protein, or an exogenous peptide; A method of treating a disease in a subject, comprising:
[Invention 2]
The method of invention 1, wherein the composition further comprises a therapeutic agent.
[Invention 3]
3. The method of invention 2, wherein the therapeutic agent comprises at least one of a small RNA, a small molecule drug, a peptide, a virus, or a combination thereof.
[Invention 4]
The method according to invention 2, wherein the therapeutic agent comprises a chemotherapeutic agent.
[Invention 5]
A method of controlling immune activation in a subject comprising administering to the subject enucleated cells that have been genetically engineered to activate the immune system.
[Invention 6]
6. The method of invention 5, wherein the enucleated cell is genetically engineered to express at least one exogenous protein.
[Invention 7]
The method according to invention 6, wherein the exogenous protein is a cell surface protein.
[Invention 8]
8. The method according to invention 7, wherein the exogenous protein is an immune activation protein.
[Invention 9]
the exogenous protein comprises a cytokine, IL-12, calreticulin, phosphatidylysin, phagocytic prey binding domain, annexin 1, OX40/OC40L, 4-1BB, B7 family member, or a combination thereof; The method according to any one of inventions 6 to 8.
[Invention 10]
A method of controlling immune recognition in a subject comprising administering to the subject enucleated cells that have been genetically engineered to evade recognition by the immune system.
[Invention 11]
11. The method of invention 10, wherein the enucleated cells are genetically engineered to deplete immune recognition molecules from the enucleated cells.
[Invention 12]
12. The method of invention 11, wherein the immune recognition molecule comprises an HLA antigen, a proteoglycan, a sugar moiety, an embryonic antigen, or a combination thereof.
[Invention 13]
11. The method of invention 10, wherein the enucleated cell is genetically engineered to express at least one exogenous protein.
[Invention 14]
The method according to invention 13, wherein the exogenous protein is a cell surface protein.
[Invention 15]
The method according to invention 13, wherein the exogenous protein is an immune evasion molecule.
[Invention 16]
The exogenous protein may include cytokines, IL-1, IL-4, IL-6, IL-8, IL-10, TGF-β, IGF-2, VEGF, TNF-alpha, CD47, HLA-E, HLA- G, HLA-E/G, PD-1, PD-L1, TIGIT, CD112R, CTLA-4, chemokine, chemokine ligand 1, C-C motif chemokine receptor 7, NK inhibitory receptor, HLA-class I specific 16. The method of invention 15, comprising an inhibitory receptor, killer cell immunoglobulin-like receptor (KIR), NKG2A, lymphocyte activation gene-3 (LAG-3), or a combination thereof.
[Invention 17]
administering to the subject enucleated cells genetically engineered to express at least one of an exogenous DNA molecule, an exogenous RNA molecule, an exogenous protein, or an exogenous peptide;
A method of identifying the presence of a disease condition in a subject, wherein said genetically engineered enucleated cells identify the presence or location of a disease condition.
[Invention 18]
18. The method according to invention 17, wherein the exogenous protein is an inflammatory homing receptor.
[Invention 19]
19. The method according to invention 18, wherein the inflammatory homing receptor directs the enucleated cells to damaged and/or inflamed tissue.
[Invention 20]
The enucleated cells are derived from natural killer (NK) cells, macrophages, neutrophils, fibroblasts, and adult stem cells, mesenchymal stromal cells (MSCs), induced pluripotent stem cells, or combinations thereof. , the method according to any one of inventions 1 to 19.
[Invention 21]
The method according to invention 20, wherein the enucleated cells are derived from mesenchymal stromal cells (MSCs).
[Invention 22]
22. The method according to any one of inventions 1 to 21, wherein the exogenous DNA molecule comprises single-stranded DNA, double-stranded DNA, oligonucleotides, plasmids, bacterial DNA molecules, DNA viruses, or combinations thereof.
[Invention 23]
Any of inventions 1 to 22, wherein the exogenous RNA molecule comprises messenger RNA (mRNA), small interfering RNA (siRNA), micro RNA (miRNA), short hairpin RNA (shRNA), RNA virus, or a combination thereof. The method described in one of the above.
[Invention 24]
24. The method according to any one of inventions 1 to 23, wherein the exogenous protein comprises a cytokine, growth factor, hormone, antibody, enzyme, or a combination thereof.
[Invention 25]
25. The method of any one of inventions 1-24, wherein said step of administering comprises intravenous administration, subcutaneous administration, intraperitoneal administration, rectal administration, oral administration, or a combination thereof.
[Invention 26]
26. The method of invention 25, wherein said step of administering comprises intratumoral administration.
[Invention 27]
According to any one of inventions 1 to 26, the disease comprises inflammation, infection, cancer, neurological disease, autoimmune disease, cardiovascular disease, ophthalmological disease, skeletal disease, metabolic disease, or a combination thereof. the method of.
[Invention 28]
the cancer comprises multiple myeloma, glioblastoma, lymphoma, leukemia, mesothelioma, sarcoma, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, colon cancer, or a combination thereof; The method according to invention 27.
Claims (20)
前記組合せ医薬が、複数の除核細胞を含む治療有効量の静脈内製剤と、少なくとも１つの免疫チェックポイント阻害剤の治療有効量とを含み、
前記複数の除核細胞のうちの少なくとも１つの除核細胞が、ポリペプチドを含み、前記ポリペプチドが、前記少なくとも１つの除核細胞に外因性のｍＲＮＡに由来の、前記少なくとも１つの除核細胞によって発現されるサイトカインを含む、
前記組合せ医薬。 1. A pharmaceutical combination for use in the treatment of cancer, comprising:
the pharmaceutical combination comprises a therapeutically effective amount of an intravenous formulation comprising a plurality of enucleated cells and a therapeutically effective amount of at least one immune checkpoint inhibitor;
At least one enucleated cell of the plurality of enucleated cells comprises a polypeptide, the polypeptide comprising a cytokine expressed by the at least one enucleated cell derived from an mRNA exogenous to the at least one enucleated cell.
The combination drug .
前記複数の除核細胞のうちの少なくとも１つの除核細胞が、サイトカインを含むポリペプチドを含み、at least one enucleated cell of said plurality of enucleated cells comprises a polypeptide comprising a cytokine;
前記ポリペプチドが、少なくとも１つの免疫チェックポイント阻害剤の治療有効量を含む併用療法として対象に投与されるように製剤化されており、the polypeptide is formulated to be administered to a subject as a combination therapy with a therapeutically effective amount of at least one immune checkpoint inhibitor;
前記治療用組成物が、静脈内投与用に製剤化されており、the therapeutic composition is formulated for intravenous administration;
前記併用療法が、前記対象のがんを治療するために治療的に有効である、the combination therapy is therapeutically effective to treat cancer in the subject;
前記治療用組成物。The therapeutic composition.
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| US62/971,526 | 2020-02-07 | ||
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| US202062994598P | 2020-03-25 | 2020-03-25 | |
| US62/994,598 | 2020-03-25 | ||
| PCT/US2021/016919 WO2021158991A1 (en) | 2020-02-07 | 2021-02-05 | Methods and use for bioengineering enucleated cells |
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| AU2022364731A1 (en) * | 2021-10-12 | 2024-05-02 | Cytonus Therapeutics, Inc. | Systems and methods for manufacturing of therapeutic cells |
| WO2024039899A2 (en) * | 2022-08-19 | 2024-02-22 | Chromatic Technologies, Inc. | Heat seal indicator |
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| US20020142397A1 (en) * | 2000-12-22 | 2002-10-03 | Philippe Collas | Methods for altering cell fate |
| CN102458458B (en) * | 2009-04-17 | 2016-11-16 | 全球免疫股份有限公司 | Combination immunotherapy compositions against cancer and method |
| EP3546485A1 (en) * | 2013-05-10 | 2019-10-02 | Whitehead Institute for Biomedical Research | In vitro production of red blood cells with sortaggable proteins |
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| AU2018316166A1 (en) * | 2017-08-07 | 2020-02-06 | The Regents Of The University Of California | Platform for generating safe cell therapeutics |
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