CN105154402B - A kind of culture medium and its application, cultural method - Google Patents
A kind of culture medium and its application, cultural method Download PDFInfo
- Publication number
- CN105154402B CN105154402B CN201510719086.8A CN201510719086A CN105154402B CN 105154402 B CN105154402 B CN 105154402B CN 201510719086 A CN201510719086 A CN 201510719086A CN 105154402 B CN105154402 B CN 105154402B
- Authority
- CN
- China
- Prior art keywords
- cell
- culture
- culture medium
- car
- cultural method
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
Landscapes
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The present invention relates to technical field of cell culture, more particularly to a kind of culture medium and its application, cultural method.The culture medium includes transferrins, rh-insulin, progesterone, fetal calf serum, stem cell factor, vitamin C, interleukin-22, IL-4, zinc sulfate and DMEM/F12 culture mediums.Culture medium of the present invention can improve the proliferation times of cell when cultivating CD19 CAR T cells, extend cell culture number of days, and can keep the surface markers such as expression CD19CAR.
Description
Technical field
The present invention relates to technical field of cell culture, more particularly to a kind of culture medium and its application, cultural method.
Background technology
Shell type lymthoma (Mantle cell lymphoma) belongs to one kind of non-Hodgkin lymphoma (NHL), about
70% patient has been in III phases or IV phase lesion in diagnosis.Clinically classical CHOP (cyclophosphamide+Doxorubicin+length
Spring new alkali+prednisone) scheme is dissatisfied to the treatment curative effect of shell type lymthoma, and only a few patients reach complete incidence graph, therefore
There is an urgent need for new therapeutic strategies to improve curative effect.
With the development of tumor immunology theory and technology, adoptive cellular immunotherapy achieve in recent years it is considerable into
Step, wherein with the tumor target that the T cell of Chimeric antigen receptor (chimericantigen receptor, CAR) modification is representative
Achievement to immunization therapy is especially prominent, in vitro with good targeting, lethal and persistence are shown in clinical test,
Illustrate huge application potential and development prospect.
The principle of CAR-T cell therapies is the T cell modified through Chimeric antigen receptor, can specifically identify tumour
Related antigen keeps the immunocyte of the more conventional application of targeting, killing activity and the persistence of effector T cell high, and can gram
It takes tumor by local immunosupress microenvironment and breaks host immune tolerance status, that is, express the T cell of CAR and relied on antigen, is non-
The mode combination tumour antigen of MHC limitations, starts and activation specific kills tumor response.
By extracellular antigen binding domain, (origin is derived from the light chain VL and heavy chain of monoclonal antibody to most of Chimeric antigen receptors
VH, it is intermediate through the hinge area with toughness connect the single-chain antibody to be formed (single chain fragment variable,
ScFv), trans-membrane region and intracellular signal transduction district's groups at.
There are many CAR types for Malignancy being currently being deployed, mainly including the use of anti-CD19, anti-
The T cell or NK cells of the antibody constructions such as CD20, anti-Kappa light chains, anti-CD22, anti-CD23, AntiCD3 McAb 0, anti-CD70 CAR modifications
Antitumor research is carried out, the achievement that the CAR built based on moderate resistance CD19 monoclonal antibodies is clinically obtained is the most prominent.
The T cell (CD19-CAR-T) for targeting the mosaic antigen acceptor gene modification of CD19 molecules is multiple, intractable in treatment
Immense success, the clinical examination of the research group of Univ Pennsylvania USA are obtained in acute lymphoblastic leukemia (ALL)
It tests the results show that up to 90% or more intractable, recurrent ALL patient obtain complete incidence graph.
Song De is just in document within 2011《Express the tumour adoptive immunity of the T cell mediateds of mosaic antigen receptor
The preclinical study of therapeutic effect》It is middle to use RPMI1640+10%FBS medium culture CAR-T cells.But use RPMI1640
+ 10%FBS goes the T cell after culture transfection, and there are shortcomings：
1, the T cell after transfecting can not be largely proliferated, because will appear the risk of gene loss, usual CD4+And CD8+Carefully
Born of the same parents' proliferation times are at 50 times or so；
2, cultivated days are limited, are typically only capable to culture 7 days or so；
3, the expression of the Chimeric antigen receptor of cell can decrease after cultivating, by taking the T cell for transfecting CD19CAR as an example,
Even if transfection efficiency reaches 90% or more, the cell proportion that CD19CAR is expressed after being generally incubated 7 days can be down to 60% or so.
Therefore, be badly in need of providing it is a kind of can effectively facilitate CAR-T cell Proliferations and can high efficient expression CAR culture medium and its
Cultural method.
Invention content
In view of this, the present invention provides a kind of culture medium and its application, cultural methods.The culture medium is in culture CD19-
When CAR-T cells, the proliferation times of cell can be improved, extend cell culture number of days, and the tables such as expression CD19CAR can be kept
Face marker.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
The present invention provides a kind of culture mediums, including transferrins, rh-insulin, progesterone, fetal calf serum, stem cell
Growth factor, vitamin C, interleukin-22, IL-4, zinc sulfate and DMEM/F12 culture mediums.
Preferably, culture medium is calculated with 1L, including following component：
In some embodiments provided by the invention, culture medium is calculated with 1L, including following component：
In other embodiments provided by the invention, culture medium is calculated with 1L, including following component：
In other embodiments provided by the invention, culture medium is calculated with 1L, including following component：
The present invention also provides the culture mediums to promote CAR-T cell Proliferations, extend cell culture time, holding expression table
Application in the marker of face；The culture medium include transferrins, rh-insulin, progesterone, fetal calf serum, stem cell growth because
Son, vitamin C, interleukin-22, IL-4, zinc sulfate and DMEM/F12 culture mediums；Preferably, culture medium is calculated with 1L, packet
Include following component：
Preferably, CAR-T cells be CD19-CAR-T, CD20-CAR-T, κ light chain-CAR-T, CD22-CAR-T,
CD23-CAR-T, CD30-CAR-T or CD70-CAR-T.
Preferably, CAR-T cells are CD19-CAR-T.
In some embodiments provided by the invention, surface marker CD4+、CD8+Or one kind or several in CD19CAR
Kind.
Preferably, surface marker is CD19CAR.
The present invention also provides a kind of cultural methods of CAR-T cells, using medium culture CAR-T cells of the present invention；
The culture medium includes transferrins, rh-insulin, progesterone, fetal calf serum, stem cell factor, vitamin C, interleukin
2, IL-4, zinc sulfate and DMEM/F12 culture mediums；Preferably, culture medium is calculated with 1L, including following component：
In some embodiments provided by the invention, which includes the following steps：
Step 1：CAR-T cells and CD3 monoclonal antibodies are added in culture medium of the present invention, cell density is adjusted, is carried out
Cell culture, supplemented medium and CD3 monoclonal antibodies after culture 72 hours；
Step 2：Continue culture at least 4 days, every 2~3 days supplementing culture mediums.
Preferably, cell density is (1~10) × 106cell/mL。
Preferably, the condition of cell culture is 5%CO2、37℃。
Preferably, a concentration of 20~50ng/mL of CD3 monoclonal antibodies.
In some embodiments provided by the invention, a concentration of 30ng/mL of CD3 monoclonal antibodies.
In some embodiments provided by the invention, which includes the following steps：
CD19-CAR-T cells culture medium of the present invention is resuspended, while the CD3 monoclonal antibodies of 30ng/mL are added, is adjusted
Whole inoculum density 1 × 106Cell/mL is put into 5%CO2, cultivate in 37 DEG C of incubators；
According to 5 × 10 after cultivating 72 hours5The density of cell/mL adds culture medium of the present invention, while adding 30ng/mL's
CD3 monoclonal antibodies；
Supplement culture medium of the present invention is primary within every 2~3 days later, keeps cell density 5 × 105cell/mL。
The present invention provides a kind of culture medium and its application, cultural methods.The culture medium includes transferrins, recombined human pancreas
Island element, progesterone, fetal calf serum, stem cell factor, vitamin C, interleukin-22, IL-4, zinc sulfate and DMEM/F12 trainings
Support base.The present invention at least has one of following advantage：
Culture medium of the present invention can improve the proliferation times of cell when cultivating CD19-CAR-T cells；
Culture medium of the present invention can extend cell culture number of days, and cultivated days can reach 21 days；
Culture medium of the present invention can keep expression CD4+、CD8+, the surface markers such as CD19CAR.
Description of the drawings
Fig. 1 shows growth curve of 1 culture medium of embodiment when cultivating CD19-CAR-T cells；
Fig. 2 shows growth curve of the comparison culture medium when cultivating CD19-CAR-T cells.
Specific implementation mode
The invention discloses a kind of culture medium and its application, cultural method, those skilled in the art can use for reference in this paper
Hold, is suitably modified technological parameter realization.In particular, it should be pointed out that all similar substitutions and modifications are to those skilled in the art
For be it will be apparent that they are considered as being included in the present invention.The method of the present invention and application are by preferably implementing
Example is described, related personnel obviously can not depart from the content of present invention, in spirit and scope to method described herein and
Using being modified or suitably changing and combine, to realize and apply the technology of the present invention.
Term is explained：
Chimeric antigen receptor (CAR)：It is the core component of CAR-T, assigns the non-dependent modes of T cell HLA and identify tumour
The ability of antigen, this enables the T cell being transformed by CAR to be identified widely compared to nave T cell surface receptor TCR
Target.The basic engineering of CAR includes the combined area a tumor associated antigen (tumor-associated antigen, TAA)
(the scFV sections for being typically derived from monoclonal antibody antigen calmodulin binding domain CaM), an extracellular hinge area, a transmembrane region and a born of the same parents
Interior signaling zone.The selection of target antigen is next for the specificity of CAR, validity and the safety of itself of genetic modification T cell
Say it is all crucial determinant.
CAR-T cells：Chimeric antigen receptor T cell.
CD19-CAR-T：Target the T cell of the mosaic antigen acceptor gene modification of CD19 molecules.
CD3：In immunology, the co-receptor of CD3 (differentiation cluster 3) T cell is a kind of protein complex, it by four not
Same chain.In mammals, the compound is containing there are one CD3 γ chains, CD3 δ chains and 2CD3 ε chains.These chains, which have, to be referred to as
One molecule pair T cell receptor (TCR) and ζ-chain are to generate the T lymphocytes of activation signal.The TCR, ζ chain and CD3 molecules one
Act the tcr complex constituted.
Used medium component, cell can be purchased by market in culture medium provided by the invention and its application, cultural method
.
With reference to embodiment, the present invention is further explained：
The preparation of 1 culture medium of embodiment
Culture medium prescription is as shown in table 1：
1 culture medium prescription of table
| Components Name | Concentration range |
| Transferrins | 100ng/mL |
| Rh-insulin | 3mg/mL |
| Progesterone | 20nmol/L |
| Fetal calf serum | 5% volume fraction |
| CSF (stem cell factor) | 20ng/mL |
| Vitamin C | 1.5mg/mL |
| Interleukin-22 (IL-2) | 50ng/mL |
| IL-4 (IL-16) | 30ng/mL |
| Zinc sulfate | 100ng/mL |
| DMEM/F12 culture mediums | Complement to 500mL |
Culture medium preparation method：Above-mentioned culture medium each component is mixed in proportion, 4 DEG C shake mixing 1 hour, then pass through
0.22 μm of membrane filtration degerming is for use.
The preparation of 2 culture medium of embodiment
Culture medium prescription is as shown in table 2：
2 culture medium prescription of table
| Components Name | Concentration range |
| Transferrins | 40ng/mL |
| Rh-insulin | 5mg/mL |
| Progesterone | 8nmol/L |
| Fetal calf serum | 3% volume fraction |
| CSF (stem cell factor) | 40ng/mL |
| Vitamin C | 0.5mg/mL |
| Interleukin-22 (IL-2) | 70ng/mL |
| IL-4 (IL-16) | 10ng/mL |
| Zinc sulfate | 200ng/mL |
| DMEM/F12 culture mediums | Complement to 500mL |
Culture medium preparation method：Above-mentioned culture medium each component is mixed in proportion, 4 DEG C shake mixing 1 hour, then pass through
0.22 μm of membrane filtration degerming is for use.
The preparation of 3 culture medium of embodiment
Culture medium prescription is as shown in table 3：
3 culture medium prescription of table
| Components Name | Concentration range |
| Transferrins | 180ng/mL |
| Rh-insulin | 0.5mg/mL |
| Progesterone | 60nmol/L |
| Fetal calf serum | 2% volume fraction |
| CSF (stem cell factor) | 5ng/mL |
| Vitamin C | 5mg/mL |
| Interleukin-22 (IL-2) | 15ng/mL |
| IL-4 (IL-16) | 80ng/mL |
| Zinc sulfate | 50ng/mL |
| DMEM/F12 culture mediums | Complement to 500mL |
Culture medium preparation method：Above-mentioned culture medium each component is mixed in proportion, 4 DEG C shake mixing 1 hour, then pass through
0.22 μm of membrane filtration degerming is for use.
4 cell culture of embodiment
1, the T cell for the expression Chimeric antigen receptor CD19CAR that Ji'nan University gives is resuspended with 1 culture medium of embodiment, together
When be added 30ng/mL CD3 monoclonal antibodies, adjust inoculum density 1 × 106Cell/mL is put into 5%CO2, cultivate in 37 DEG C of incubators.
2, according to 5 × 10 after cultivating 72 hours5The density of cell/mL adds 1 culture medium of embodiment, while adding 30ng/
The CD3 monoclonal antibodies of mL.
3, it is primary that the culture medium was supplemented per 2-3 days later, keeps cell density 5 × 105cell/mL；
4, the growth curve of cell is calculated, and culture to 7 days and 21 days cells is taken to carry out flow cytometer detection.
Cell detection is specially：The cell being collected into is cleaned 2 times with PBS, its surface marker is detected by streaming instrument
CD4+, CD8+And the expression rate of CD19CAR.
The T cell of CD19CAR is cultivated according to above-mentioned steps using culture medium made from embodiment 2 or embodiment 3,
Detection.
Comparative example 1 is set, and the concrete operations of comparative example 1 are：The expression Chimeric antigen receptor CD19CAR that Ji'nan University gives
T cell be added RPMI1640+10%FBS, adjust inoculum density 1 × 106Cell/mL is put into 5%CO2, in 37 DEG C of incubators
Culture；It is primary per fluid infusion in 2-3 days later, keep cell density 5 × 105cell/mL；The growth curve of cell is calculated, and is taken
The cell cultivated by 7 days and 21 days carries out flow cytometer detection.
Comparative example 2 is set, and the concrete operations of comparative example 2 are：The expression Chimeric antigen receptor CD19CAR that Ji'nan University gives
T cell RPMI1640+10%FBS is added, while the CD3 monoclonal antibodies of 30ng/mL are added, adjust inoculum density 1 × 106cell/
ML is put into 5%CO2, cultivate in 37 DEG C of incubators；According to 5 × 10 after cultivating 72 hours5The density of cell/mL adds RPMI1640
+ 10%FBS, while adding the CD3 monoclonal antibodies of 30ng/mL；Per 2-3 days, supplement RPMI1640+10%FBS was primary later, kept thin
Born of the same parents' density is 5 × 105cell/mL；The growth curve of cell is calculated, and culture to 7 days and 21 days cells is taken to carry out streaming inspection
It surveys.
5, test result：
5.1, cell proliferative conditions
4 are shown in Table to the proliferation number of the T cell culture of CD19CAR using 1 to 3 culture medium of embodiment and comparison culture medium, in fact
It applies 1 growth curve of example and sees Fig. 1, the growth curve of embodiment 2,3 and this is close.Comparative example growth curve is shown in Fig. 2.
The proliferation number of the T cell culture of table 4CD19CAR
By above-mentioned test result as it can be seen that culture medium provided by the invention can effectively facilitate the proliferation of the T cell of CD19CAR.
5.2, flow cytometer detection result
Flow cytometer detection the results are shown in Table 5：
5 flow cytometer detection result of table
Culture medium produced by the present invention can improve the proliferation times of cell when cultivating CD19-CAR-T cells, extend
Cell culture number of days, and expression CD19CAR can be kept.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (8)
1. a kind of CD19-CAR-T cell culture mediums, which is characterized in that by transferrins, rh-insulin, progesterone, tire ox blood
Clearly, stem cell factor, vitamin C, interleukin-22, IL-4, zinc sulfate and DMEM/F12 culture mediums composition；
The CD19-CAR-T cell culture mediums are calculated with 1L, and the content of each component is：
2. culture medium as described in claim 1 is promoting CD19-CAR-T cell Proliferations, is extending cell culture time, holding table
Up to the application in surface marker.
3. application according to claim 2, which is characterized in that the surface marker is CD4+、CD8+Or in CD19CAR
One or more.
4. a kind of cultural method of CD19-CAR-T cells, which is characterized in that use medium culture as described in claim 1
CD19-CAR-T cells.
5. cultural method according to claim 4, which is characterized in that include the following steps：
Step 1：CD19-CAR-T cells and CD3 monoclonal antibodies are added in culture medium as described in claim 1, cell is adjusted
Density, carries out cell culture, and culture adds the culture medium and the CD3 monoclonal antibodies after 72 hours；
Step 2：Continue culture at least 4 days, the culture medium was supplemented every 2~3 days.
6. cultural method according to claim 5, which is characterized in that the cell density is (1~10) × 106cell/
mL。
7. cultural method according to claim 5, which is characterized in that the condition of the cell culture is 5%CO2、37℃。
8. cultural method according to claim 5, which is characterized in that a concentration of the 20 of the CD3 monoclonal antibodies~
50ng/mL。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510719086.8A CN105154402B (en) | 2015-10-28 | 2015-10-28 | A kind of culture medium and its application, cultural method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510719086.8A CN105154402B (en) | 2015-10-28 | 2015-10-28 | A kind of culture medium and its application, cultural method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105154402A CN105154402A (en) | 2015-12-16 |
| CN105154402B true CN105154402B (en) | 2018-09-21 |
Family
ID=54795449
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510719086.8A Active CN105154402B (en) | 2015-10-28 | 2015-10-28 | A kind of culture medium and its application, cultural method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105154402B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106148279A (en) * | 2016-07-28 | 2016-11-23 | 广州赛莱拉干细胞科技股份有限公司 | A kind of method of long-time cultivation B cell |
| CN109053899B (en) * | 2017-12-22 | 2021-11-16 | 湖南远泰生物技术有限公司 | Chimeric antigen receptor containing human transferrin antigen epitope sequence |
| CN108949696A (en) * | 2018-08-21 | 2018-12-07 | 苏州米苏生物技术有限公司 | Immune cell media is applied with it |
| CN109055311B (en) * | 2018-08-21 | 2022-03-15 | 苏州沃美生物有限公司 | Human lymphocyte culture method based on serum-free culture medium |
| CN111154720B (en) * | 2020-01-14 | 2020-12-25 | 南京鼓楼医院 | CAR-T culture medium and application thereof |
| CN115786273A (en) * | 2023-02-07 | 2023-03-14 | 赛尔医学科技(山东)有限公司 | Culture method of targeting CAR-T cells |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102925411A (en) * | 2012-11-30 | 2013-02-13 | 中山大学 | Application of vitamin C in in-vitro expansion of number of effector memory T cells |
| CN104371972A (en) * | 2013-08-12 | 2015-02-25 | 英普乐孚生物技术(上海)有限公司 | T lymphocyte culture medium without any animal original or human original component and preparation method thereof |
-
2015
- 2015-10-28 CN CN201510719086.8A patent/CN105154402B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102925411A (en) * | 2012-11-30 | 2013-02-13 | 中山大学 | Application of vitamin C in in-vitro expansion of number of effector memory T cells |
| CN104371972A (en) * | 2013-08-12 | 2015-02-25 | 英普乐孚生物技术(上海)有限公司 | T lymphocyte culture medium without any animal original or human original component and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| IL-4 and IL-2 Promote Human T-Cell Proliferation through Symmetrical but Independent Pathways;REUVEN OR et al.;《CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY》;19920930;第64卷(第3期);摘要 * |
| 孕酮对人T淋巴细胞体外活化CD69表达的作用;孙荭等;《中国免疫学杂志》;20001231;第16卷(第12期);第677页第3节 * |
| 维生素C对CD4+效应记忆性T细胞体外扩增的影响;张译文等;《中国病理生理杂志》;20131231;第29卷(第8期);摘要 * |
| 表达嵌合性抗原受体的T淋巴细胞介导的肿瘤过继性免疫治疗作用的临床前研究;宋德刚;《中国博士学位论文全文数据库 医药卫生科技辑》;20120615(第06期);第95-96页第2.2节 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105154402A (en) | 2015-12-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105154402B (en) | A kind of culture medium and its application, cultural method | |
| JP7542270B2 (en) | Methods and compositions for cellular immunotherapy | |
| US12029761B2 (en) | Guidance and Navigation Control proteins and method of making and using thereof | |
| CN106414748B (en) | Chimeric antigen receptor and method of preparation | |
| JP6290751B2 (en) | Methods and compositions for increasing the effectiveness of therapeutic antibodies using NK cell enhancing compounds | |
| JP7098325B2 (en) | CS1 targeted chimeric antigen receptor modified T cells | |
| CN105073776B (en) | For treating the preparation of the Cancerous disease of expression tight junction protein | |
| JP2019041772A (en) | IDENTIFICATION OF CD8+ T CELLS THAT ARE CD161hi AND/OR IL18Rahi AND HAVE RAPID DRUG EFFLUX CAPACITY | |
| CN109280086B (en) | Hypoxia-inducible chimeric antigen receptor specifically activated by tumor microenvironment | |
| CN108779174A (en) | Target the Chimeric antigen receptor of HER2 | |
| Hoseini et al. | Bispecific antibody does not induce T-cell death mediated by chimeric antigen receptor against disialoganglioside GD2 | |
| AU2014268364A1 (en) | Chimeric antigen receptor-targeting monoclonal antibodies | |
| CA3118616A1 (en) | Selection of improved tumor reactive t-cells | |
| CA3177394A1 (en) | Method and compositions for cellular immunotherapy | |
| JP2022533621A (en) | Engineered immune cells containing recognition molecules | |
| CN107207580A (en) | Anti- CLDN Chimeric antigen receptors and application method | |
| CN108368159A (en) | Chimeric antigen receptor containing catilan domain | |
| WO2020248486A1 (en) | Method for preparing car-t that uses tcm as main effective ingredient and use thereof | |
| Guo et al. | Effective antitumor activity of 5T4‐specific CAR‐T cells against ovarian cancer cells in vitro and xenotransplanted tumors in vivo | |
| US20230272341A1 (en) | Multifunctional immune effector cell and use thereof | |
| TW202003853A (en) | Genetically modified cell and producing method therefor | |
| Nakagawa et al. | Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy | |
| Yoon et al. | Transfer of Her-2/neu specificity into cytokine-induced killer (CIK) cells with RNA encoding chimeric immune receptor (CIR) | |
| CN109306340A (en) | A kind of artificial antigen presenting cell and application thereof of the full T cell of efficient amplification | |
| Marton et al. | Homeostatic cytokines tune naivety and stemness of cord blood-derived transgenic T cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |