WO2018214943A1 - 一种冻存细胞制剂及细胞复苏方式 - Google Patents

一种冻存细胞制剂及细胞复苏方式 Download PDF

Info

Publication number
WO2018214943A1
WO2018214943A1 PCT/CN2018/088246 CN2018088246W WO2018214943A1 WO 2018214943 A1 WO2018214943 A1 WO 2018214943A1 CN 2018088246 W CN2018088246 W CN 2018088246W WO 2018214943 A1 WO2018214943 A1 WO 2018214943A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
cell
preparation
frozen
cryopreservation
Prior art date
Application number
PCT/CN2018/088246
Other languages
English (en)
French (fr)
Chinese (zh)
Inventor
张丽
王飞
何佳平
林南静
刘丽萍
刘欣
李超
余舒倩
胡永来
赵佳维
孙哲
刘晓雨
Original Assignee
西比曼生物科技（上海）有限公司
西比曼生物科技（无锡）有限公司
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 西比曼生物科技（上海）有限公司, 西比曼生物科技（无锡）有限公司 filed Critical 西比曼生物科技（上海）有限公司
Priority to AU2018272688A priority Critical patent/AU2018272688B2/en
Priority to US16/616,216 priority patent/US20200170242A1/en
Priority to EP18805534.7A priority patent/EP3632207A4/en
Priority to JP2020515812A priority patent/JP7303184B2/ja
Priority to NZ759568A priority patent/NZ759568A/en
Priority to KR1020197038096A priority patent/KR102350423B1/ko
Publication of WO2018214943A1 publication Critical patent/WO2018214943A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/125—Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators
    • 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
    • A61K40/00—Cellular immunotherapy
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • 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
    • A61K40/42—Cancer antigens
    • A61K40/428—Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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

Definitions

  • the present invention belongs to the field of cell therapy, and in particular, the present invention provides a no-washable intravenously inoculated frozen cell preparation, and simplifies the use of the frozen cell preparation.
  • Fresh cells are typically used for intravenous or topical infusion, or cryopreserved cells are washed and used.
  • Fresh cells usually have an expiration date of less than 8 hours before clinical use, which is not conducive to long-distance transportation, and can not adapt to changes in clinical patients. Therefore, if it is necessary to apply to cells in the therapeutic field, it is bound to involve the process of cryopreservation and resuscitation of cells.
  • cryopreservation in the laboratory, resuscitation washing of frozen cells is usually performed in a clean environment (such as in a sterile room) and requires the operation of a professional biotech technician.
  • a clean environment such as in a sterile room
  • the process of cryopreservation is carried out in a general hospital, unable to provide a sterile room environment, and lack of personnel with corresponding experimental skills, which limits the promotion of cell therapy.
  • the invention adopts a no-clean cryopreservation solution for preparation of a cell frozen preparation, and the cell resuscitation and dilution can be carried out for clinical use by a simple dispensing operation. Effectively solve the above problems in the field of cell therapy.
  • a cryopreserved (frozen) cell preparation comprising:
  • a cryopreservation solution comprising: an aqueous solution of sodium chloride, a protective protein, and dimethyl sulfoxide.
  • the cell is a cell selected from the group consisting of a primary T cell, a T cell after expansion, a T cell after gene transduction, a stem cell, or a combination thereof.
  • the cells are cells selected from the group consisting of suspension cultured cells and adherent cultured cells.
  • the adherent cultured cells are pre-digested and suspended prior to preparation of the cryopreserved preparation.
  • the cell density ranges from 1 ⁇ 10 5 to 5 ⁇ 10 8 /ml.
  • the sodium chloride concentration in the preparation is from 0.85% to 0.95% (w/v).
  • the protective protein concentration is from 10% to 90% (w/v) in the formulation.
  • the protective protein has a protective protein concentration of 10-30% (w/v).
  • the protective protein concentration of the formulation is 15-25% (w/v).
  • the dimethyl hydrazine concentration is from 5% to 40% (v/v) in the formulation.
  • the concentration of dimethyl hydrazine in the preparation is from 5% to 20% (v/v).
  • the dimethyl hydrazine concentration is 8% to 12% (v/v) in the preparation.
  • the method comprises the steps of:
  • the frozen diluent comprises the following components: An aqueous solution of sodium chloride, and a protective protein;
  • the container is a frozen or frozen tube.
  • the cryopreservation diluent comprises: an aqueous solution of sodium chloride, and a protective protein.
  • the sodium chloride concentration in the cryopreservation diluent is from 0.85% to 0.95% (w/v).
  • the concentration of the protective protein in the cryopreserved diluent is from 10% to 90% (w/v).
  • the protective protein has a protective protein concentration of 10-30% (w/v).
  • the protective protein concentration of the formulation is 15-25% (w/v).
  • a cryopreservation cell resuscitation method comprising the steps of:
  • the resuscitation further comprises the steps of: detecting the viability of the cells, and if the viability meets the requirements for use, for clinical use.
  • the thermostatic device is a thermostatic water bath.
  • the cell thawing time is from 30 seconds to 3 minutes.
  • the injection carrier is an intravenously injectable solution, preferably selected from the group consisting of sodium chloride injection, compound electrolyte injection, and amino acid injection.
  • Figure 1 is a graph showing changes in cell viability before and after cryopreservation in Example 1;
  • Figure 2 is a graph showing the cell proliferation ability after cryopreservation in Example 1;
  • Figure 3 is a graph showing the comparison of tumor antigen response ability of CAR-T cells before and after cryopreservation in Example 1;
  • Figure 4 shows a comparison of different cryopreservation methods (programs).
  • the inventors designed a simple cell cryopreservation-recovery method and the corresponding cryopreservation solution used.
  • the method can be conveniently performed by a medical professional in an ordinary laboratory environment, and thus can be used as a cryopreservation-recovery method in a cell therapy process. Based on the above findings, the inventors completed the present invention.
  • freeze cell preparation and “freeze cell preparation” are used interchangeably and refer to a preparation containing therapeutically active cells that is preserved at low temperatures (eg, at -80 ° C, or in a liquid nitrogen environment).
  • the cryopreserved (frozen) cell preparation of the present invention comprises the following components:
  • a cryopreservation solution comprising: an aqueous solution of sodium chloride, a protective protein, and dimethyl sulfoxide.
  • the cell is an active cell which can be used for cell therapy, and the kind thereof is not particularly limited.
  • the cell is a cell selected from the group consisting of primary T cells, after expansion and culture. T cells, T cells after gene transduction, stem cells, or a combination thereof.
  • the cell type of the present invention is not particularly limited, and in another preferred embodiment, the cell is a cell selected from the group consisting of a suspension cultured cell and an adherent cultured cell.
  • the adherent cultured cells are pre-digested and suspended prior to preparation of the cryopreserved preparation.
  • the cell density range is not particularly limited and may be, for example, 1 ⁇ 10 5 - 5 ⁇ 10 8 /ml.
  • the sodium chloride concentration is from 0.85% to 0.95% (w/v).
  • the protective protein concentration of the formulation is from 10% to 90% (w/v).
  • the dimethyl hydrazine concentration is from 5% to 40% (v/v) in the formulation.
  • the invention also provides a method for cryopreservation-recovery of cells, the method comprising the steps of:
  • the frozen diluent comprises the following components: An aqueous solution of sodium chloride, and a protective protein;
  • the ratio of the above two may be slightly different depending on the type of cells to be frozen.
  • the container is not particularly limited, and is preferably a container which can pierce the surface of the container with a syringe to perform liquid absorption.
  • the container is a frozen or frozen tube.
  • cryopreserved cells can be resuscitated in a conventional non-sterile environment.
  • the resuscitation process comprises the steps of:
  • the resuscitation further comprises the steps of: detecting the viability of the cells, and if the viability meets the requirements for use, for clinical use.
  • the constant temperature device is not particularly limited and may be a thermostatic device commonly used in a laboratory (such as a constant temperature water bath).
  • the cell thawing time is from 30 seconds to 3 minutes.
  • the injection carrier is not particularly limited, and may preferably be an intravenously solution, more preferably selected from the group consisting of sodium chloride injection, compound electrolyte injection, and amino acid injection.
  • the collected cells are washed with physiological saline prior to cryopreservation to ensure that the residues meet the clinical use requirements of the product.
  • the cryopreservation diluent has the same composition as the cryopreservation solution except that it does not contain dimethyl sulfoxide. According to the cryopreservation specification, resuspend the cells with the frozen diluent to make the cell concentration 2 times the final concentration, and then slowly add an equal volume of the cryopreservation solution and mix well. The cell suspension was transferred to a cryopreservation bag (or a cryotube), and the temperature was lowered using a cooling rate of 1-2 ° C / min. When cooling to below 80 °C, transfer to a liquid nitrogen refrigerator for storage.
  • the frozen preparation was taken out from the liquid nitrogen refrigerator at the time of use, and quickly thawed at 37 °C. After thawing, transfer to physiological saline with an injection or a single use connector.
  • the live cell assay was performed on the diluted cell preparation. The live rate meets the requirements for use and is used clinically.
  • the cell preparation prepared by the present invention can maintain a high cell viability after long-term storage, and is convenient for long-distance transportation from a preparation unit to a hospital.
  • the cell cryopreservation preparations according to the present invention all use adjuvant-grade or pharmaceutical-grade reagents, and can be safely applied in clinical practice.
  • the resuscitation operation of the frozen cell preparation by the use mode of the present invention can eliminate the stringent requirements of the cell preparation operation on the aseptic environment, and can enable an untrained nurse to easily grasp the recovery of the frozen cells. Maintain high cell viability.
  • the resuscitation operation of the frozen cell preparation by the use mode of the present invention can maintain the biological activity of the cells.
  • the frozen storage container of the frozen cell preparation is a frozen storage bag.
  • the cell type is CAR-T cells. Freeze the specifications 2 ⁇ 10 7 /10ml.
  • the components of the frozen cell preparation are shown in the table below.
  • the CAR-T cells were frozen for 3 months with 100 ml, and then thawed in a 37 ° C water bath for 2 minutes, and the thawed cells were diluted with a syringe into 100 ml of physiological saline. The diluted cells were taken for viability assay, tumor antigen response assay and cell proliferation assay.
  • Cell viability changes The diluted cell suspension was tested for viability by trypan blue staining and the results are shown in Figure 1. The results showed that the cells maintained a high survival rate after resuscitation.
  • Proliferative capacity of cells after cryopreservation The cryopreserved cells were placed in complete medium and cultured, and the density of the cells was recorded daily. The medium was supplemented every 2-3 days and a growth curve was drawn (as shown in Figure 2). It can be seen from the figure that after the cryopreservation process, the cells still have better proliferative capacity.
  • the tumor antigen response ability of CAR-T cells before and after cryopreservation cryopreserved cells and tumor cells carrying tumor antigen were co-cultured for 1:1 overnight, and the culture supernatant was collected to detect the amount of IFNr released by CAR-T cells; The ratio of CD137 positive cells expressing CD137 was used to assess tumor antigen response ability.
  • the data before cryopreservation and the data which were further cultured for 7 days after cryopreservation were compared as shown in Fig. 3. The results showed that the cell's tumor antigen response capacity did not decrease significantly after undergoing the cryopreservation-resuscitation process.
  • the frozen cell preparation survival rate after cryopreservation for 3 months is over 90%.
  • the reconstituted frozen CAR-T cell preparation still has value-adding capabilities.
  • the resuscitated frozen CAR-T cell preparation has a reversible decrease in tumor antigen response ability and is restored after continued culture.
  • the frozen cell preparation maintains the original potency of fresh cells and can be used clinically.
  • the cells were rapidly thawed in 37 ° C waters and transferred to pre-warmed DMEM at 37 ° C, and about 0.3 ml was taken for viability detection.
  • the results showed that after the cell cryopreservation and resuscitation using the method of the present application, the recovery rate was higher than that of the cryopreservation recovery method using the cryopreservation method of the control group.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Environmental Sciences (AREA)
  • Dentistry (AREA)
  • Inorganic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
PCT/CN2018/088246 2017-05-24 2018-05-24 一种冻存细胞制剂及细胞复苏方式 WO2018214943A1 (zh)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU2018272688A AU2018272688B2 (en) 2017-05-24 2018-05-24 Cell cryopreservation formulation and cell recovery method
US16/616,216 US20200170242A1 (en) 2017-05-24 2018-05-24 Cell cryopreservation formulation and cell recovery method
EP18805534.7A EP3632207A4 (en) 2017-05-24 2018-05-24 FORMULATION FOR CELL PRESERVATION AND CELL RECOVERY METHOD
JP2020515812A JP7303184B2 (ja) 2017-05-24 2018-05-24 凍結保存細胞製剤および細胞再生方法
NZ759568A NZ759568A (en) 2017-05-24 2018-05-24 Cell cryopreservation formulation and cell recovery method
KR1020197038096A KR102350423B1 (ko) 2017-05-24 2018-05-24 세포 동결 보존 제제 및 세포 소생 방법

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201710375424.X 2017-05-24
CN201710375424.XA CN108925548A (zh) 2017-05-24 2017-05-24 一种冻存细胞制剂及细胞复苏方式

Publications (1)

Publication Number Publication Date
WO2018214943A1 true WO2018214943A1 (zh) 2018-11-29

Family

ID=64396262

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/088246 WO2018214943A1 (zh) 2017-05-24 2018-05-24 一种冻存细胞制剂及细胞复苏方式

Country Status (8)

Country Link
US (1) US20200170242A1 (eng)
EP (1) EP3632207A4 (eng)
JP (1) JP7303184B2 (eng)
KR (1) KR102350423B1 (eng)
CN (1) CN108925548A (eng)
AU (1) AU2018272688B2 (eng)
NZ (1) NZ759568A (eng)
WO (1) WO2018214943A1 (eng)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023109846A (ja) * 2020-03-31 2023-08-08 Ｃｅｌｌ Ｅｘｏｓｏｍｅ Ｔｈｅｒａｐｅｕｔｉｃｓ株式会社 細胞の保存方法

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110679588A (zh) * 2019-10-23 2020-01-14 厦门生命互联科技有限公司 一种嵌合抗原受体t细胞冻存介质及用途
US20220354108A1 (en) * 2021-05-04 2022-11-10 Tissue Testing Technologies Llc Preservation methods using trehalose with other cryoprotectants being absent from the cryopreservation protocol
CN113994951A (zh) * 2021-11-17 2022-02-01 晋文娟 一种cik细胞冻存液及冻存方法
CN114097771B (zh) * 2021-12-15 2022-10-14 珠海贝索细胞科学技术有限公司 一种细胞保存液及其应用和细胞保存方法
CN115136955A (zh) * 2022-08-03 2022-10-04 深圳宾德生物技术有限公司 细胞冻存液及其制备方法和应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040067480A1 (en) * 2002-10-04 2004-04-08 Organ Recovery Systems, Inc. Method for treatment of cellular materials with sugars prior to preservation
CN102907416A (zh) * 2012-08-01 2013-02-06 臻景生物技术（上海）有限公司 一种可维持细胞活性的组织冻存液
CN103461322A (zh) * 2012-06-07 2013-12-25 臻景生物技术（上海）有限公司 用于冻存复苏后的细胞的保存液
CN103583511A (zh) * 2012-09-03 2014-02-19 四川新生命干细胞科技股份有限公司 一种间充质干细胞冻存液及注射液
CN104430301A (zh) * 2014-11-18 2015-03-25 成都康华生物制品有限公司 一种提高人二倍体细胞存活率的方法
CN105325402A (zh) * 2015-11-13 2016-02-17 黄林海 一种用于玻璃化冻存骨髓间充质干细胞的冻存保护剂
CN105477017A (zh) * 2015-12-03 2016-04-13 深圳爱生再生医学科技有限公司 治疗糖尿病足的混合干细胞制剂及其制备方法
CN105660606A (zh) * 2016-03-10 2016-06-15 广州赛莱拉干细胞科技股份有限公司 一种细胞冻存液

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6713245B2 (en) * 1998-07-06 2004-03-30 Diacrin, Inc. Methods for storing neural cells such that they are suitable for transplantation
US20030054331A1 (en) * 2001-09-14 2003-03-20 Stemsource, Inc. Preservation of non embryonic cells from non hematopoietic tissues
US7176022B2 (en) * 2002-12-20 2007-02-13 Cell Genesys, Inc. Directly injectable formulations which provide enhanced cryoprotection of cell products
US20070025961A1 (en) 2003-06-03 2007-02-01 Kenzo Bamba Composition for stabilizing survival of transplanted hematopoietic stem cell, kit for obtaining the composition, method of stabilizing survival of transplanted hematopoietic stem cell, human monoclonal antibody or human polyclonal antibody and method of producing the same, gene encoding human monoclonal antibody and transf
CN102119936B (zh) * 2011-03-07 2012-12-12 李荣旗 制备利用人羊膜间充质细胞治疗缺血性脑损伤注射液的方法及其注射液
CN102908364A (zh) * 2012-11-14 2013-02-06 青岛奥克生物开发有限公司 一种间充质干细胞注射液及其制备方法和在制备治疗儿童扩张型心肌病药物中的应用
BR112016009753B1 (pt) 2013-11-04 2023-11-28 Isopogen Pty Ltd Métodos in vitro de cultura de amostras de células estromais mesenquimais e para a preparação de células estromais mesenquimais
AU2015288052B2 (en) 2014-07-07 2021-12-16 Targazyme, Inc. Manufacture and cryopreservation of fucosylated cells for therapeutic use
US20180116956A1 (en) * 2015-04-02 2018-05-03 Stegi-Ra Trust Composition for use in treating celiac disease
CN104873542A (zh) * 2015-05-21 2015-09-02 北京青藤谷禧干细胞科技研究院有限公司 一种脐带间充质干细胞注射液及其制备方法和应用
CN104857022A (zh) * 2015-05-21 2015-08-26 北京青藤谷禧干细胞科技研究院有限公司 一种间充质干细胞注射液、制备方法及其应用
CN105394026B (zh) * 2015-10-31 2017-09-29 北京军科联合干细胞生物科技有限公司 一种造血干细胞冻存新方法
CN106177918A (zh) * 2016-09-30 2016-12-07 广州赛莱拉干细胞科技股份有限公司 一种间充质干细胞注射液及其制备方法和应用
WO2018071405A1 (en) * 2016-10-11 2018-04-19 University Of Miami Vectors and vaccine cells for immunity against zika virus
CN106665560B (zh) * 2017-01-16 2021-02-05 哈尔滨医科大学 一种直接静脉回输的免疫细胞冻存液及其应用

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040067480A1 (en) * 2002-10-04 2004-04-08 Organ Recovery Systems, Inc. Method for treatment of cellular materials with sugars prior to preservation
CN103461322A (zh) * 2012-06-07 2013-12-25 臻景生物技术（上海）有限公司 用于冻存复苏后的细胞的保存液
CN102907416A (zh) * 2012-08-01 2013-02-06 臻景生物技术（上海）有限公司 一种可维持细胞活性的组织冻存液
CN103583511A (zh) * 2012-09-03 2014-02-19 四川新生命干细胞科技股份有限公司 一种间充质干细胞冻存液及注射液
CN104430301A (zh) * 2014-11-18 2015-03-25 成都康华生物制品有限公司 一种提高人二倍体细胞存活率的方法
CN105325402A (zh) * 2015-11-13 2016-02-17 黄林海 一种用于玻璃化冻存骨髓间充质干细胞的冻存保护剂
CN105477017A (zh) * 2015-12-03 2016-04-13 深圳爱生再生医学科技有限公司 治疗糖尿病足的混合干细胞制剂及其制备方法
CN105660606A (zh) * 2016-03-10 2016-06-15 广州赛莱拉干细胞科技股份有限公司 一种细胞冻存液

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3632207A4 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2023109846A (ja) * 2020-03-31 2023-08-08 Ｃｅｌｌ Ｅｘｏｓｏｍｅ Ｔｈｅｒａｐｅｕｔｉｃｓ株式会社 細胞の保存方法
JP7546968B2 (ja) 2020-03-31 2024-09-09 Ｃｅｌｌ Ｅｘｏｓｏｍｅ Ｔｈｅｒａｐｅｕｔｉｃｓ株式会社 細胞の保存方法

Also Published As

Publication number Publication date
EP3632207A1 (en) 2020-04-08
AU2018272688A1 (en) 2019-12-19
JP2020520680A (ja) 2020-07-16
EP3632207A4 (en) 2021-03-10
KR102350423B1 (ko) 2022-01-11
KR20200073171A (ko) 2020-06-23
NZ759568A (en) 2023-01-27
US20200170242A1 (en) 2020-06-04
CN108925548A (zh) 2018-12-04
JP7303184B2 (ja) 2023-07-04
AU2018272688B2 (en) 2021-05-27

Similar Documents

Publication Publication Date Title
WO2018214943A1 (zh) 一种冻存细胞制剂及细胞复苏方式
CN107148967B (zh) 一种抗原特异性t淋巴细胞冻存液及其制备方法和应用
CN106665560B (zh) 一种直接静脉回输的免疫细胞冻存液及其应用
CN103563888B (zh) 细胞冻存液
CN108207930B (zh) 一种鸡尾酒式冷冻保护剂及其应用
WO2018113796A1 (zh) 一种可临床使用的细胞冻存液
CN110959606B (zh) 一种免疫效应细胞冻存液及其用途
CN108552160A (zh) 一种直接静脉回输的car-t细胞冻存液及其制备方法和应用
JP6531256B2 (ja) 臍帯血および末梢血の凍結保存方法および凍結保存用溶液
CN104430303B (zh) 人外周血干细胞冻存液的配制及使用方法
CN105941389A (zh) 一种无动物源血清的细胞冻存液
CN109315386A (zh) 一种可用于造血干细胞或淋巴细胞的冻存液及冻存方法
CN112167240A (zh) 临床级细胞冷藏保存液及其制备方法和应用
CN116998475A (zh) 一种用于新鲜肿瘤组织保存和运输的组织保存液及应用
CN107711823B (zh) 一种常温保存的细胞冻存液及其应用
CN114403127B (zh) 一种间充质干细胞冷藏保护液及保存方法
CN101914497B (zh) 临床用n-cik细胞培养、质量控制鉴定试剂盒及应用
WO2021190620A1 (zh) 细胞保存液及其试剂盒
CN107912425B (zh) 一种可输液的细胞冻存管试剂盒及其应用
EP4156926A1 (en) Cryopreserving macrophages
HK40017286A (en) Cell cryopreservation formulation and cell recovery method
CN110679588A (zh) 一种嵌合抗原受体t细胞冻存介质及用途
WO2018214942A1 (zh) 一种冻存细胞试剂盒
WO2023038037A1 (ja) 細胞の処理方法
CN110882276B (zh) 细胞治疗组合物及治疗血管病变的方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18805534

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2020515812

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2018272688

Country of ref document: AU

Date of ref document: 20180524

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2018805534

Country of ref document: EP

Effective date: 20200102

WWW Wipo information: withdrawn in national office

Ref document number: 2018805534

Country of ref document: EP