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 PDFInfo
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- 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
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- Prior art keywords
- cells
- cell
- preparation
- frozen
- cryopreservation
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- 238000005138 cryopreservation Methods 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 32
- 238000009472 formulation Methods 0.000 title claims abstract description 18
- 238000011084 recovery Methods 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 claims abstract description 53
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 26
- 239000003085 diluting agent Substances 0.000 claims abstract description 20
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 20
- 230000001681 protective effect Effects 0.000 claims abstract description 18
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 18
- 239000011780 sodium chloride Substances 0.000 claims abstract description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 238000007710 freezing Methods 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 106
- 239000000243 solution Substances 0.000 claims description 15
- 239000007924 injection Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 210000004748 cultured cell Anatomy 0.000 claims description 8
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 claims description 5
- 230000001464 adherent effect Effects 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000003792 electrolyte Substances 0.000 claims description 3
- 210000004986 primary T-cell Anatomy 0.000 claims description 3
- 239000008354 sodium chloride injection Substances 0.000 claims description 3
- 210000000130 stem cell Anatomy 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 229940102223 injectable solution Drugs 0.000 claims description 2
- 238000010790 dilution Methods 0.000 abstract description 2
- 239000012895 dilution Substances 0.000 abstract description 2
- 230000008014 freezing Effects 0.000 abstract description 2
- 238000005406 washing Methods 0.000 abstract description 2
- 239000012595 freezing medium Substances 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000002659 cell therapy Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 238000010257 thawing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 2
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- 230000007774 longterm Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
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- 238000001514 detection method Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Images
Classifications
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- 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
- A01N1/02—Preservation of living parts
-
- 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
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0221—Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464499—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
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- 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.
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Abstract
Description
序号 | 组分 | 含量 |
1 | 细胞 | 2×10 7/ml |
2 | 氯化钠 | 0.9%(w/v) |
3 | 人血清白蛋白 | 20%(w/v) |
4 | 二甲基亚砜 | 10%(v/v) |
Claims (10)
- 一种冻存(冰冻)细胞制剂,其特征在于,所述制剂包括:(1)细胞;(2)冻存液,所述的冻存液包括:氯化钠水溶液、保护性蛋白,和二甲基亚砜。
- 如权利要求1所述的制剂,其特征在于,所述的细胞为选自下组的细胞:原代T细胞、扩增培养后的T细胞、基因转导后的T细胞、干细胞,或其组合。
- 如权利要求1所述的制剂,其特征在于,所述的细胞为选自下组的细胞:悬浮培养的细胞和贴壁培养的细胞。
- 如权利要求1所述的制剂,其特征在于,所述的制剂中,细胞密度范围是1×10 5-5×10 8/ml。
- 如权利要求1所述的制剂,其特征在于,所述的制剂中,氯化钠浓度为0.85%-0.95%(w/v)。
- 如权利要求1所述的制剂,其特征在于,所述的制剂中,保护性蛋白浓度为10%-90%(w/v)。
- 如权利要求1所述的制剂,其特征在于,所述的制剂中,二甲基亚矾浓度为5%-40%(v/v)。
- 如权利要求1所述的制剂的制备方法,其特征在于,所述方法包括步骤:(a)提供待冻存的细胞和冻存稀释液,用所述的冻存稀释液重悬所述细胞,得到第一冻存混合物;其中,所述的冻存稀释液包括以下组分:氯化钠水溶液,和保护性蛋白;(b)在所述的第一冻存混合物中加入冻存稀释液,混匀,得到第二冻存混合物;(c)转移所述的第二冻存混合物至容器中,进行程序降温至-80℃以下,得到所述的冻存细胞制剂。
- 一种冻存细胞复苏方法,其特征在于,包括步骤:(i)提供如权利要求1中所述的冻存细胞制剂;(ii)将所述的冻存细胞制剂置于35-40℃的恒温设备中进行复苏,得到复苏后的细胞-冻存液复合物;(iii)用注射器或一次性使用连接器将所述制剂中的细胞转移至注射载体中。
- 如权利要求9所述的方法,其特征在于,所述的注射载体为可静脉注射的溶液,优选地选自下组:氯化钠注射液、复方电解质注射液、氨基酸注射液。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ759568A NZ759568A (en) | 2017-05-24 | 2018-05-24 | Cell cryopreservation formulation 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 |
KR1020197038096A KR102350423B1 (ko) | 2017-05-24 | 2018-05-24 | 세포 동결 보존 제제 및 세포 소생 방법 |
EP18805534.7A EP3632207A4 (en) | 2017-05-24 | 2018-05-24 | FORMULATION FOR CELL PRESERVATION AND CELL RECOVERY METHOD |
AU2018272688A AU2018272688B2 (en) | 2017-05-24 | 2018-05-24 | Cell cryopreservation formulation and cell recovery method |
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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 |
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 |
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KR20200073171A (ko) | 2020-06-23 |
JP7303184B2 (ja) | 2023-07-04 |
EP3632207A4 (en) | 2021-03-10 |
AU2018272688A1 (en) | 2019-12-19 |
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