CN110016465A - A kind of immunocyte drug comprising B cell and the double identity T cells of tumour - Google Patents
A kind of immunocyte drug comprising B cell and the double identity T cells of tumour Download PDFInfo
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Abstract
It is including in the tumours identity T cells such as TIL, neoantigen reaction-ive T cell the present invention provides a kind of Chimeric antigen receptor (B-CAR) cross-film expression that will target B cell, preparation includes the immune cell therapy drug of " B cell & tumour --- double identity T cells ", pass through the identification to normal B cells in vivo by the B-CAR structure of the drug, it realizes the internal stimulation to " B cell & tumour --- double identity T cells " and substantially expands, to solve the quantity bottleneck problem of tumour identity T cell.The present invention can become a kind of immunocyte medicinal application in the antineoplaston for not distinguishing cancer kind.
Description
Technical field
The invention belongs to biomedicine technical fields, and specifically the present invention provides a kind of immune cell therapy drug, this
Kind cell drug solves the quantity bottleneck problem of tumour identity T cell.
Background technique
T cell is the main force of immunotherapy of tumors, and the curative effect of immunotherapy of tumors, which depends greatly on, to be known
The number of the quantity of the T cell of other tumour.There are many technological means at present to collect tumour identity T cell, including from
It is separated in tumor tissues tumor-infiltrated T lymphocyte (TIL), or tumour neoantigen is obtained by high-flux sequence
(neoantigen) to screen neoantigen reaction-ive T cell, etc..
Under normal circumstances, late tumor patient it is intracorporal it is naturally occurring can specific recognition tumour and can collected T
Cell --- TIL or neoantigen reaction-ive T cell is either come from, total quantity is compared with tumour cell total amount, all
It is seldom, it is possible to differ 4 orders of magnitude (ten thousand times) or more.
On the other hand, either neoantigen reaction-ive T cell or TIL, are impossible to infinitely expand in vitro,
And repetitious stimulation amplification is easy that T cell state is made to enter depletion state too early, to seriously affect its therapeutic effect, this point
More so for TIL.
Therefore either TIL or neoantigen therapy all suffer from tumour identity T cell quantity limitation problem, this is for this
Class tumour immunotherapy is bottleneck problem very serious and puzzlement.
On the other hand, show targeting from the clinical data to a large amount of CD19 CAR-T for controlling B cell neoplastic hematologic disorder
The CAR-T cell for the antigen that the B cells such as CD19, CD20, CD22 are generally expressed, can massive amplification in vivo.It can be seen that borrowing
The environment for helping the similar vaccine of the B cell of the extensive magnanimity of patient's body, target the T cell of the CAR of B cell can be big in vivo
Amount amplification.
Summary of the invention
The purpose of the clinical research of above-mentioned CAR-T is to treat B cell neoplastic hematologic disorder, and essence of the invention is by B cell
Treatment to the effect of CAR-T substantially expanded, as the auxiliary amplification system of tumour identity T cell, applied to solid tumor
In.
The present invention passes through the CAR expression that will target B cell in tumour identity T cell, preparation " B cell & tumour ---
Double identity T cells ", the bottleneck that solving the problems, such as.
It is to have tomour specific identity that the premise of identity T cells double first, which is this kind of T cell, this is base of the invention
Plinth condition, i.e., will first collect the tumour identity T cell of patient, then do the genetic modification of the CAR of targeting B cell.
Genetic modification can be realized by systems such as slow virus.The tumour identity T cell for being transferred to CAR is that " B is thin
Born of the same parents' & tumour --- double identity T cells ".
Why this kind of T cell is referred to as double identities, is because this kind of T cell both can be by identifying tumour neoantigen
Start the killing to tumour, and can be by identifying that B cell starts the killing to normal B cells.In the same of killing B cell
When, this kind of tumour identity T cell i.e. massive amplification in vivo, to be able to more effective killing tumor cell.
It is that this kind of double identity T cell drugs are possible to killing normal B cells that the present invention, which is applied to clinical unique risk,
Lead to patient body fluid immunodeficiency, but this risk is limited: first when no longer needing double identity T cells in vivo
When, double identity T cells can be removed by the design using the expression regulation in CAR structure or switch element of committing suiside, from
And terminate its killing to B cell；Patient can make up this defect by exogenous supplement immunoglobulin, and mostly
Patient can restore the regeneration of B cell in 2~12 months；On the other hand, compared with the tumor disease of life-threatening, two evils are mutually weighed
Take it light, the risk that B cell is removed can temporarily be ignored, as CAR-T technology is wide in the treatment of B cell neoplastic hematologic disorder
The situation of general application.
Attached drawing table explanation:
Expression of Fig. 1 .BCAR in TCR-T, TIL and NeoT.
External function test and amplification of Fig. 2 .BCAR in the TCR-T of targeting NY ES01 gene.
Fig. 3 .BCAR is in the external function test of TIL and amplification.
Fig. 4 .BCAR is in the external function test of NeoT and amplification.
The tumor load variation of Fig. 5 .BCAR-NY ES01-TCRT cell in animal experiments.
The tumor load variation of Fig. 6 .BCAR-TIL cell in animal experiments.
The tumor load variation of Fig. 7 .BCAR-NeoT cell in animal experiments.
Specific embodiment
In order to be more fully understood and with the application of the invention, hereinafter with reference to embodiment and attached drawing the present invention is described in detail, institute
It states embodiment to be only intended to illustrate the present invention, be limited the scope of the invention without being intended to.The scope of the present invention is by rear attached
Claim specifically limit.
Embodiment one, tumour identity T cell --- the preparation of the TCR-T cell of target tumor target spot NY-ESO-1
The present embodiment is thin with the neoantigen reactivity T of the quasi-simple target spot of TCR-T cell membrane of target tumor target spot NY-ESO-1
Born of the same parents.
Venous collection Healthy People 30ml peripheral blood, using Ficoll lymphocyte separation medium separate PBMC, adherent 2 hours,
Taking suspension cell-is mainly T cell.The TCR slow virus carrier (HLA-A:0201) of identification NY-ESO-1 is added, according to MOI
Slow virus is added in (slow virus number/cell number)=5, cultivates 72h, and airflow classification goes out the positive TCR-T cell of TCR expression, stream
Formula detects TCR positive rate 95% or more.
Embodiment two, tumour identity T cell --- the preparation of tumor-infiltrated T lymphocyte (TIL)
10 grams of specimens or more are taken, the cell of tumor tissues is isolated with enzyme digestion, and divided with CD3 magnetic bead
From the T cell for being purified into the CD3 positive, remaining cell adhere-wall culture obtains the tumour cell of autologous patient.
Embodiment three, tumour identity T cell --- the preparation of neoantigen reaction-ive T cell (neoT)
Firstly, the tumor tissues for extracting peripheral blood in patients or operation excision carry out full exon or the sequencing of rna transcription group；Choosing
Mutational site is taken, and patient HLA parting is combined to carry out affinity peptide prediction, about 20 mutation is chosen and is used as Neoantigen.Gene
The Neoantigen is synthesized, and is transcribed in vitro into RNA；Again, it singly adopts or directly extracts peripheral blood in patients, isolate PBMC
And adherent 2 hours, adherent monocytes are taken, relevant cell factor is added and promotes DC cell differentiation mature, and electricity turns RNA and enters carefully
Born of the same parents；Suspension cell, predominantly T cell are taken, the DC cell turned with electricity co-cultures, and the T cell of the separation CD137+ positive is newly resisted
Former reaction-ive T cell (following or abbreviation neoT), and expand the cell.
The preparation of the slow virus carrier of the CAR (following or abbreviation BCAR) of example IV, targeting B cell
Target of the CD19 as BCAR is chosen, CD19 CAR is constructed, represents BCAR.
CD19 CAR slow virus carrier, using safer forth generation slow virus carrier system.By main carrier CD19 CAR,
And package carrier pMDL-gag, Rev, envelope vector pMD2.G, using calcium phosphate or liposome PEI cotransfection 293T cell,
48 hours collection supernatants, and carry out ultracentrifugation concentration slow virus.
The titre of CD19 CAR slow virus carrier detects, and using 3 times of doubling dilutions, 50ul is taken to infect 293T cell, infection
It 48 hours to 72 hours, collects 293T cell and carries out CAR dyeing, the ratio of flow cytometer showed CAR+ cell, and carried out according to formula
Titre calculates:
Titre (TU/ml)=starting 293T cell number × CAR+Cell percentages × extension rate × 20 (take first PD1+
Cell percentages < 20% is calculated), calculate slow virus titre > 3 × 107It can carry out next step use.
Embodiment five, BCAR forgoing neoplasms identity T cell transfection
Aforementioned three kinds of neoantigens are added in slow virus and are known according to MOI=5 according to the CD19 CAR slow virus titre of preparation
In other property T cell (i.e. NY-ESO-1-TCR-T, TIL, neoT), BCAR-NY-ESO-1-TCR-T, BCAR-TIL are respectively obtained,
BCAR-neoT, flow cytometer detection the results show that BCAR has about 60% expression in three kinds of tumour antigen identity T cells
(Fig. 1) is cultivated respectively and is expanded three kinds of T cells.
Embodiment six, the NY-ESO1 for expressing BCAR
The external function test of TCR-T cell
In order to verify effect of the BCAR in the TCR-T of targeting NY-ESO-1, it is A that we construct HLA parting first:
The tumor cell line of 0201 J82-NY ESO1-Luc.In order to verify double identification sexual functions of BCAR-NY ESO1-TCRT, I
First 24 orifice plates be inoculated with 1 × 105The J82-NY ESO1 tumour cell of quantity is divided into 4 groups and is tested after adherent overnight,
Control group A group is added 2 × 105The T cell of quantity co-cultures；B group is added 2 × 105(positive rate of CAR is the BCAR-T of quantity
60%) it co-cultures；C group is added 2 × 105The NY-ESO1 TCR-T of quantity is co-cultured；D group is added 2 × 105The BCAR-NY- of quantity
ESO1 TCR-T is co-cultured；Meanwhile this four groups of cells are all added 5 × 104B cell, respectively detect:
1, the amplification situation of T cell.48h, 96h are co-cultured, T cell is counted respectively, as shown in Figure 2 a, by 4
It co-cultivation, A group T cell expand 3 times or so；B group BCAR-T expands about 12 times；C group NY ESO1-TCRT amplification about 10
Times；And D group BCAR-NY ESO1-TCRT amplification is at most, reaches 27 times.Experiment in vitro the result shows that, in the stimulating ring of B cell
Under border, after transfecting CD19 CAR, quantity is available substantially to be expanded TCR-T.
2, the growing state of tumour cell.After co-culturing 48h and 96h, remove supernatant, PBS is rinsed 3 times, is cracked adherent
Tumour cell, the survival rate of tumour cell is indicated using the activity of kit measurement luciferase.Fig. 2 b co-cultures 48h
Vitro Experimental Results prompt, under the environmental stimulation of B cell, after transfecting BCAR, the ability for killing tumour obviously mentions TCR-T
It is high.
Embodiment seven, express BCAR TIL external function test
In order to verify effect of the CD19 CAR in TIL, the tumour that we will separate first from patient's fresh tumor tissue
Cell inoculation is to 24 orifice plates, after adherent overnight, be separately added into TIL and BCAR-TIL and co-culture, while all dividing in hole all adds
Enter the B cell of identical quantity and detected:
1, the quantitative comparison of T cell.96h is co-cultured with tumour cell, as shown in Figure 3a,TILExpand about 10 times, and
BCAR-TIL expands about 25 times.Experiment in vitro the result shows that, under the environmental stimulation of B cell, TIL transfection CD19 CAR
Afterwards, quantity is available substantially expands.
2, the growing state of tumour cell.After co-culturing 96h, remove supernatant, PBS is rinsed 3 times, cracks adherent tumour
Cell indicates the survival rate of tumour cell using the activity of kit measurement luciferase.The Vitro Experimental Results table of Fig. 3 b
Bright, under the environmental stimulation of B cell, after transfecting BCAR, the ability for killing tumour significantly improves TIL.
Embodiment eight, express BCAR neoantigen reaction-ive T cell external functional experiment
In order to verify effect of the CD19 CAR in NeoT, the tumour that we will separate first from patient's fresh tumor tissue
Cell inoculation is to 24 orifice plates, after adherent overnight, be separately added into NeoT and BCAR-NeoT and co-culture, while all dividing in hole all
The B cell of identical quantity is added and is detected:
1, the quantitative comparison of T cell.96h is co-cultured with tumour cell, as shown in fig. 4 a, _ NeoT has expanded about 9 times, and
BCAR-NeoT expands about 23 times.Experiment in vitro the result shows that, under the environmental stimulation of B cell, NeoT transfection CD19
After CAR, quantity is available substantially to be expanded.
2, the growing state of tumour cell.After co-culturing 96h, remove supernatant, PBS is rinsed 3 times, cracks adherent tumour
Cell indicates the survival rate of tumour cell using the activity of kit measurement luciferase.The Vitro Experimental Results table of Fig. 4 b
Bright, under the environmental stimulation of B cell, after transfecting BCAR, the ability for killing tumour significantly improves NeoT.
Embodiment nine, the NY-ESO-1 for expressing B CAR
The zoopery of TCR-T cell
Animal model building: by 1 × 106The tumour cell J82-NY-ESO-1 of quantity is inoculated into NSG Mice Body,
PBS (A0) is subcutaneously injected in blank control group, injects the mouse of tumour cell, about starts tumor formation after two weeks, and measurement in the 23rd day is swollen
Tumor size, and choose 30 mouse and enter group.
Administration: blank control group (A0) tail vein injection PBS, the mouse of inoculated tumour cell are divided into 6 groups, are respectively as follows: PBS
Group (A1)；T cell group (A2)；BCAR-T groups of cells (A3)；NY-ESO-1 TCR-T groups of cells (A4)；BCAR&NY-ESO-1
The bis- identity T cell groups (A5) of TCRT；NY-ESO-1 TCR-T cell high dose group (A6).Administration mode: A1-5 group is 1 ×
104A T cell tail vein venoclysis, A6 group are 1 × 107A T cell tail vein infusion, all groups are transfused 1 × 107A B is thin
Born of the same parents.
After administration, the measurement and mouse state observation of tumor size are carried out within every 2-3 days, gross tumor volume=1/2* major diameter * is short
Diameter * minor axis, continuous observation 28 days.
One, tumor load changes:
Tumor-bearing mice upon administration one week, gross tumor volume sustainable growth the 7th day, detects that A4, A5 and A6 group tumour are opened
Beginning to reduce, but A4 group tumor regression amplitude is unobvious, and started rebound and continued growth at the 11st day, A6 group is obviously reduced,
But started to rebound at the 16th day；And A5 group is persistently contracted to almost disappear, tumour just starts to rebound within the 23rd day.Other three groups of tumours
Keep nature growth (Fig. 5).
Two, the total amount variation of the T cell being transfused in vivo:
In four groups of administration, the 10th day after administration, from 2,3,4,5 groups of extraction peripheral bloods, detected using streaming method
CD3 carries out the total amount of estimation T cell, and result is respectively 2.11 × 105, 1.91 × 107, 1.52 × 106, 5 × 107, prompt band
A3, A5 group of BCAR T cell total amount obtained shows BCAR-T cell and B cell & tumour considerably beyond A4 group ---
Double identity T cells can be expanded substantially in vivo.
Embodiment ten, express BCAR til cell zoopery
Animal model building: the 1 × 10 of fresh tumor tissue will be isolated from6The cancer cell subcutaneous of quantity is inoculated into NSG
In Mice Body, PBS (A0) is subcutaneously injected in blank control group, injects the mouse of tumour cell, about starts tumor formation after two weeks, and the 25th
Its measurement tumor size, and choose 30 mouse and enter group.
Administration: blank control group (A0) tail vein injection PBS, the mouse of inoculated tumour cell are divided into 5 groups, are respectively as follows: not
Administration-PBS group (A1)；T cell group (A2)；BCAR-T groups of cells (A3)；Til cell group (A4)；BCAR-TIL groups of cells
(A5).Administration mode: A1~5 group are 1 × 104A T cell tail vein infusion, all groups are transfused 1 × 107A B cell.It gives
After medicine, the measurement and mouse state observation of tumor size are carried out within every 2-3 days, gross tumor volume=1/2* major diameter * minor axis * minor axis is held
Continuous observation 28 days.
One, tumor load changes:
Tumor-bearing mice upon administration one week, gross tumor volume sustainable growth the 6th day, detects that A4, A5 group tumour start to contract
It is small, but A4 group tumor regression amplitude is unobvious, and starts rebound and continued growth at the 14th day, and A5 group is persistently contracted to almost disappear
It loses, tumour just starts to rebound within the 21st day.Other three groups of tumours keep nature to grow (Fig. 6).
Two, the total amount variation of the T cell being transfused in vivo:
In four groups of administration, the 10th day after administration, from 2,3,4,5 groups of extraction peripheral bloods, detected using streaming method
CD3 carries out the total amount of estimation T cell.Its result is respectively 1.87 × 105, 1.57 × 107, 9.52 × 106, 3 × 107, prompt band
A3, A5 group of BCAR T cell total amount obtained shows BCAR-T cell and B cell & tumour considerably beyond A4 group ---
Double identity T cells can be expanded substantially in vivo.
Embodiment ten, express BCAR neoantigen reaction-ive T cell zoopery
Animal model building: the 1 × 10 of fresh tumor tissue will be isolated from6Cancer cell subcutaneous is inoculated into NSG Mice Body
Interior, PBS (A0) is subcutaneously injected in blank control group, injects the mouse of tumour cell, about starts tumor formation after two weeks, measures within the 23rd day
Tumor size, and choose 30 mouse and enter group.
Administration: blank control group (A0) tail vein injection PBS, the mouse of inoculated tumour cell are divided into 6 groups, are respectively as follows: not
Administration-PBS group (A1)；T cell group (A2)；BCAR-T groups of cells (A3)；Common neoT groups of cells (A4)；BCAR-neoT is bis- to be known
Other property T cell group (A5)；Common neoT cell high dose group (A6).Administration mode: A1~5 group are 1 × 104A T cell tail
Cava vein infusion, A6 group are 1 × 107A T cell tail vein infusion, all groups are transfused 1 × 107A B cell.
After administration, the measurement and mouse state observation of tumor size are carried out within every 2-3 days, gross tumor volume=1/2* major diameter * is short
Diameter * minor axis, continuous observation 28 days.
One, tumor load changes:
Tumor-bearing mice upon administration one week, gross tumor volume sustainable growth the 9th day, detects that A4, A5 and A6 group tumour are opened
Begin to reduce, but A4 group the 11st day rebounds, A6 group started to rebound at the 18th day；And A5 group is persistently contracted to almost disappear, the 23rd day
Tumour just starts to rebound.Other three groups of tumours keep nature to grow (Fig. 7).
Two, the total amount variation of the T cell being transfused in vivo:
In four groups of administration, the 10th day after administration, from 2,3,4,5 groups of extraction peripheral bloods, detected using streaming method
CD3 carries out the total amount of estimation T cell.Its result is respectively 1.65 × 105, 1.23 × 107, 1,02 × 107, 3.15 × 107, mention
Show that the T cell total amount obtained of A3, A5 group with BCAR considerably beyond A4 group, shows that BCAR-T cell and B cell & are swollen
Tumor --- double identity T cells can be expanded substantially in vivo.
Above-mentioned B cell & tumour --- double identity T cells animal experiments show that:
1.B cell & tumour --- double identity T cells can stimulate realization substantially to expand by B cell.
The double identity T cells of A6 group can be expanded substantially in vivo, reach the quantity with CAR-T cell same order.
2. being equally low dose of feedback, B cell & tumour --- double identity T cells can obtain better curative effect.
After the double identity T cells of A5 group substantially expand in vivo, the effect that tomour specific killing is remarkably reinforced can be played,
The tumour identity T cell group that the remote ultra small dose of effect is fed back, possibly even more comparable to large dosage of tumour identity T cell group
By force.
Statistics indicate that B cell & tumour --- double identity T cells can be expanded rapidly in Mice Body and be realized obvious swollen
It is all remote super to give same low dose and give tumour identity T cell in tumor inhibitory effect, either expanding effect or curative effect
Group.
Claims (5)
1. a kind of immunocyte preparation method is prepared " B cell & tumour --- double identity T cells ", it is characterised in that:
1) Chimeric antigen receptor (following or abbreviation " B-CAR " or " BCAR ") expression of B cell surface protein will be targeted in tumour
Identity T cell；
2) Chimeric antigen receptor (B-CAR) of the targeting B cell surface protein includes following characteristics:
A.B cell surface protein includes the memebrane protein of CD19, CD20, CD22 and other any B cell wide expressions:
B. the B-CAR structure includes the variable region of the antibody of CD3 ζ and the above-mentioned B cell surface protein of targeting；
C. the B-CAR structure may include the costimulatory molecules and other genes or protein modified including CD28,41BB,
It can not include these costimulatory molecules and other genes or protein modified；
D. the B-CAR structure may include or not include TET-ON or other any one CAR or CAR-T cell expression regulations
And enable the element of the switch of CAR-T cell suicide or apoptosis；
E. the B-CAR structure includes or not comprising the antibody variable region for targeting CD19, sequence such as sequence table SEQ ID NO:1
It is shown
3) the tumour identity T cell can be the clone's of a variety of TCR sequences obtained by any one method of following ABC
T cell mixture, or by grouping screening high flux screening after single or a variety of TCR sequences clone T cell:
A. from tumor tissues separate tumor infiltrating lymphocyte (TIL) and obtain, progress or without the further expansion to TIL
Increase, be transformed or to include but is not limited to any one or a few molecule such as PD1, CD137, TIM3 as the screening of marker；
B. one or more of markers such as T cell progress PD1, CD137, TIM3 in human peripheral blood are screened and are obtained, or into
It goes or without to its further amplification or transformation；
C. it is obtained tumour neoantigen (neoantigen) through oncogene sequencing analysis somatic mutation, and passes through any means,
It obtains tumour identity T cell and obtains, and the TCR serial processing of the tumour identity T cell of single clone is thin to general T
Born of the same parents and obtain, the samples sources of the gene sequencing include that any one can be obtained to tumor tissues and ctDNA and excretion body etc.
The sequencing samples sources of tumoral character variation, sequencing approach is sequenced including customization Panel, full exon, full transcript profile is sequenced,
Immune group library sequencing etc. any one can obtain tumoral character variation sequencing strategy and method.
2. method as described in claim 1, which is characterized in that the B-CAR or immunologic test point-costimulating factor shifting molecular
In the B cell & tumour --- the expression of double identity T cells or tumour identity T cell, can by it is following any one or
Accomplished in many ways:
1) with slow virus or adenovirus or adeno-associated virus etc., any one can pierce altogether the B-CAR or immunologic test point-
The transfection of factor shifting molecular is swashed in the transfection carrier or medium of the tumour identity T cell genome and stable expression and side
Method or system and realize；
2) B-CAR or the electric shock transfection of immunologic test point-costimulating factor shifting molecular mRNA sequence are entered described swollen
It is realized in tumor identity T cell.
3. a kind of immune cell therapy drug or pharmaceutical composition, which is characterized in that in the drug or pharmaceutical composition research and development, life
Produce, preparation, application any one during used immunocyte preparation method described in claims 1 or 2, or to making
The cell that the method described in claims 1 or 2 is prepared is expanded or is carried out the working process of other experimental methods, and its
Any one in therapeutic agent, treatment method derives application.
4. immune cell therapy drug as claimed in claim 3 or pharmaceutical composition, which is characterized in that the drug or medicine group
Close the application in any cancer kind or disease, the antineoplaston of any neoplasm staging.
5. cellular therapeutic agent as claimed in claim 3 or pharmaceutical composition, which is characterized in that at it applied to oncotherapy
In mechanism, on the one hand by the cell drug or pharmaceutical composition to the specific recognition of tumour and killing tumor cell, another party
Face makes by the identification of " B cell & tumour --- double identity T cells " to B cell in the cell drug or pharmaceutical composition
It obtains " B cell & tumour --- double identity T cells " to be expanded by the stimulation of B cell, to enhance the cell drug or medicine
Object combines the killing ability to tumour.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810017770.5A CN110016465A (en) | 2018-01-09 | 2018-01-09 | A kind of immunocyte drug comprising B cell and the double identity T cells of tumour |
| CN201880072560.4A CN111542595B (en) | 2017-11-10 | 2018-11-12 | Modified immune cells and uses thereof |
| JP2020544095A JP2021502114A (en) | 2017-11-10 | 2018-11-12 | Modified immune cells and their use |
| US15/733,076 US11866731B2 (en) | 2017-11-10 | 2018-11-12 | Modified immune cells and uses thereof |
| EP18877126.5A EP3707248A4 (en) | 2017-11-10 | 2018-11-12 | Modified immune cells and uses thereof |
| PCT/CN2018/115079 WO2019091478A1 (en) | 2017-11-10 | 2018-11-12 | Modified immune cells and uses thereof |
| JP2023000285A JP2023036929A (en) | 2017-11-10 | 2023-01-04 | Modified immune cells and uses thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810017770.5A CN110016465A (en) | 2018-01-09 | 2018-01-09 | A kind of immunocyte drug comprising B cell and the double identity T cells of tumour |
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| Publication Number | Publication Date |
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| CN110016465A true CN110016465A (en) | 2019-07-16 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020164465A1 (en) | 2019-02-11 | 2020-08-20 | 北京卡替医疗技术有限公司 | Adjuvant capable of promoting expansion of immune cells in vivo |
| CN114121142A (en) * | 2021-09-02 | 2022-03-01 | 四川大学华西医院 | Novel gene modification enhanced NY-ESO-1 special TCR-T model construction method and application |
| WO2022089443A1 (en) * | 2020-10-26 | 2022-05-05 | 北京卡替医疗技术有限公司 | Modified immune cell and use thereof |
| CN114555788A (en) * | 2019-09-06 | 2022-05-27 | 阿维塔斯有限公司 | Immune cell engineering for in vitro cell therapy |
-
2018
- 2018-01-09 CN CN201810017770.5A patent/CN110016465A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020164465A1 (en) | 2019-02-11 | 2020-08-20 | 北京卡替医疗技术有限公司 | Adjuvant capable of promoting expansion of immune cells in vivo |
| CN114555788A (en) * | 2019-09-06 | 2022-05-27 | 阿维塔斯有限公司 | Immune cell engineering for in vitro cell therapy |
| WO2022089443A1 (en) * | 2020-10-26 | 2022-05-05 | 北京卡替医疗技术有限公司 | Modified immune cell and use thereof |
| CN114121142A (en) * | 2021-09-02 | 2022-03-01 | 四川大学华西医院 | Novel gene modification enhanced NY-ESO-1 special TCR-T model construction method and application |
| CN114121142B (en) * | 2021-09-02 | 2023-10-31 | 四川大学华西医院 | Novel gene modification enhanced NY-ESO-1 special-shaped TCR-T model construction method and application |
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Application publication date: 20190716 |