MX351226B - Celulas t con memoria central anti tercera parte, metodos para producirlas y uso de las mismas en transplante y tratamiento de enfermedades. - Google Patents

Celulas t con memoria central anti tercera parte, metodos para producirlas y uso de las mismas en transplante y tratamiento de enfermedades.

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Publication number
MX351226B
MX351226B MX2014002771A MX2014002771A MX351226B MX 351226 B MX351226 B MX 351226B MX 2014002771 A MX2014002771 A MX 2014002771A MX 2014002771 A MX2014002771 A MX 2014002771A MX 351226 B MX351226 B MX 351226B
Authority
MX
Mexico
Prior art keywords
cells
central memory
same
transplantation
antigen
Prior art date
Application number
MX2014002771A
Other languages
English (en)
Spanish (es)
Other versions
MX2014002771A (es
Inventor
Reisner Yair
Eidelstein Yaki
Ophir Eran
Lask Assaf
Afik Ran
Or-Geva Noga
Bachar-Lustig Esther
Original Assignee
Yeda Res & Dev
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yeda Res & Dev filed Critical Yeda Res & Dev
Publication of MX2014002771A publication Critical patent/MX2014002771A/es
Publication of MX351226B publication Critical patent/MX351226B/es

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/22—Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/26—Lymph; Lymph nodes; Thymus; Spleen; Splenocytes; Thymocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
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    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
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    • A61K35/38—Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
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    • A61K35/37—Digestive system
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    • A—HUMAN NECESSITIES
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    • A61K35/407—Liver; Hepatocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/42—Respiratory system, e.g. lungs, bronchi or lung cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K40/10—Cellular immunotherapy characterised by the cell type used
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    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/22—Immunosuppressive or immunotolerising
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/418—Antigens related to induction of tolerance to non-self
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K40/50—Cellular immunotherapy characterised by the use of allogeneic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2307—Interleukin-7 (IL-7)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2315—Interleukin-15 (IL-15)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2321—Interleukin-21 (IL-21)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
    • C12N2502/1121—Dendritic cells

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Physiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nutrition Science (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Mycology (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
MX2014002771A 2011-09-08 2012-09-06 Celulas t con memoria central anti tercera parte, metodos para producirlas y uso de las mismas en transplante y tratamiento de enfermedades. MX351226B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161532172P 2011-09-08 2011-09-08
PCT/IL2012/050354 WO2013035099A1 (en) 2011-09-08 2012-09-06 Anti third party central memory t cells, methods of producing same and use of same in transplantation and disease treatment

Publications (2)

Publication Number Publication Date
MX2014002771A MX2014002771A (es) 2015-02-04
MX351226B true MX351226B (es) 2017-10-05

Family

ID=47003163

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2014002771A MX351226B (es) 2011-09-08 2012-09-06 Celulas t con memoria central anti tercera parte, metodos para producirlas y uso de las mismas en transplante y tratamiento de enfermedades.

Country Status (14)

Country Link
US (3) US20140212398A1 (cg-RX-API-DMAC7.html)
EP (1) EP2753351B1 (cg-RX-API-DMAC7.html)
JP (1) JP6196620B2 (cg-RX-API-DMAC7.html)
KR (1) KR102073901B1 (cg-RX-API-DMAC7.html)
CN (1) CN103930130B (cg-RX-API-DMAC7.html)
AU (1) AU2012305931B2 (cg-RX-API-DMAC7.html)
BR (1) BR112014005355B1 (cg-RX-API-DMAC7.html)
CA (1) CA2848121C (cg-RX-API-DMAC7.html)
ES (1) ES2640813T3 (cg-RX-API-DMAC7.html)
MX (1) MX351226B (cg-RX-API-DMAC7.html)
RU (1) RU2636503C2 (cg-RX-API-DMAC7.html)
SG (1) SG11201400513PA (cg-RX-API-DMAC7.html)
WO (1) WO2013035099A1 (cg-RX-API-DMAC7.html)
ZA (1) ZA201401993B (cg-RX-API-DMAC7.html)

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ES2615861T3 (es) * 2008-10-30 2017-06-08 Yeda Research And Development Company Ltd. Células T de memoria central anti-terceros, métodos de producción de las mismas y uso de las mismas en trasplante y tratamiento de enfermedades
ES2953434T3 (es) 2009-08-24 2023-11-13 Baylor College Medicine Generación de líneas de CTL con especificidad frente a múltiples antígenos tumorales o múltiples virus
PL2613801T3 (pl) 2010-09-08 2016-12-30 Zastosowanie komórek T pamięci centralnych przeciwko obcym antygenom do leczenia białaczki/chłoniaka
MX351226B (es) 2011-09-08 2017-10-05 Yeda Res & Dev Celulas t con memoria central anti tercera parte, metodos para producirlas y uso de las mismas en transplante y tratamiento de enfermedades.
GB201121308D0 (en) 2011-12-12 2012-01-25 Cell Medica Ltd Process
US10351824B2 (en) 2011-12-12 2019-07-16 Cell Medica Limited Process of expanding T cells
EP2812431B1 (en) 2012-02-09 2019-07-17 Baylor College Of Medicine Pepmixes to generate multiviral ctls with broad specificity
SG11201407819UA (en) * 2012-06-11 2014-12-30 Wolf Wilson Mfg Corp Improved methods of cell culture for adoptive cell therapy
WO2016168595A1 (en) * 2015-04-17 2016-10-20 Barrett David Maxwell Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells
CN104946588A (zh) * 2015-07-07 2015-09-30 英普乐孚生物技术(上海)有限公司 一种抗原特异性t淋巴细胞的分离和高效扩增培养方法
US11179448B2 (en) 2015-07-16 2021-11-23 Yeda Research And Development Co. Ltd. Genetically modified anti-third party central memory T cells and use of same in immunotherapy
CA2992551A1 (en) 2015-07-21 2017-01-26 Novartis Ag Methods for improving the efficacy and expansion of immune cells
HK1258649A1 (zh) 2015-09-18 2019-11-15 Baylor College Of Medicine 来自病原体的免疫原性抗原鉴定以及与临床效力的相关性
US10691773B2 (en) 2015-12-30 2020-06-23 General Electric Company Cell processing techniques
AU2017283480A1 (en) 2016-06-13 2019-01-24 Torque Therapeutics, Inc. Methods and compositions for promoting immune cell function
CN109310746B (zh) * 2016-06-24 2023-12-05 麦克马斯特大学 过继细胞转移与溶瘤病毒组合疗法
MX2019000022A (es) * 2016-06-27 2019-09-18 Yeda Res & Dev Células veto generadas a partir de linfocitos t de memoria.
US10751368B2 (en) 2017-01-18 2020-08-25 Yeda Research And Development Co. Ltd. Methods of transplantation and disease treatment
EP3571295B1 (en) * 2017-01-18 2026-01-07 Yeda Research and Development Co. Ltd Genetically modified veto cells and use of same in immunotherapy
JP7136454B2 (ja) * 2017-01-20 2022-09-13 国立大学法人京都大学 ＣＤ８α＋β＋細胞傷害性Ｔ細胞の製造方法
JP2020511464A (ja) 2017-03-15 2020-04-16 オルカ バイオシステムズ インコーポレイテッド 造血幹細胞移植用の組成物および方法
EP3678701A4 (en) 2017-09-05 2021-12-01 Torque Therapeutics, Inc. THERAPEUTIC PROTEIN COMPOSITIONS AND METHODS FOR PREPARING AND USING THE SAME
MX2020003129A (es) * 2017-09-20 2020-10-12 Neximmune Inc Composiciones celulares que comprenden linfocitos t específicos para antígenos para una terapia adoptiva.
CN108165529B (zh) * 2017-12-28 2021-07-16 北昊干细胞与再生医学研究院有限公司 中枢记忆性t细胞体及其外培养方法
CA3090148A1 (en) * 2018-02-06 2019-08-15 Seattle Children's Hospital (dba Seattle Children's Research Institute) Closed-system manufacturing process for car-t cells
EP3809983B1 (en) 2018-06-22 2025-08-27 Mayo Foundation for Medical Education and Research Methods and materials for improving arteriovenous fistula maturation and maintaining arteriovenous fistula functionality
WO2020010259A1 (en) * 2018-07-06 2020-01-09 Mayo Foundation For Medical Education And Research Methods and materials for improving transplant outcomes
JP7495137B2 (ja) * 2018-08-10 2024-06-04 ユーティレックス カンパニー リミテッド 癌抗原特異的細胞傷害性ｔ細胞
CN109628396B (zh) * 2019-01-24 2021-03-26 清华大学 记忆性淋巴细胞群在肝癌治疗中的应用
WO2021024264A2 (en) * 2019-08-06 2021-02-11 Yeda Research And Development Co. Ltd. Anti-viral central memory cd8+ veto cells in haploidentical stem cell transplantation
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