CN109694413A - A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence - Google Patents
A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence Download PDFInfo
- Publication number
- CN109694413A CN109694413A CN201910042481.5A CN201910042481A CN109694413A CN 109694413 A CN109694413 A CN 109694413A CN 201910042481 A CN201910042481 A CN 201910042481A CN 109694413 A CN109694413 A CN 109694413A
- Authority
- CN
- China
- Prior art keywords
- bmca
- chimeric antigen
- antigen receptor
- nano antibody
- antibody sequence
- 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.)
- Pending
Links
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title claims abstract description 33
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 26
- 241001416177 Vicugna pacos Species 0.000 claims abstract description 25
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims abstract description 17
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims abstract description 17
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims abstract description 17
- 239000000427 antigen Substances 0.000 claims abstract description 16
- 108091007433 antigens Proteins 0.000 claims abstract description 16
- 102000036639 antigens Human genes 0.000 claims abstract description 16
- 229920001184 polypeptide Polymers 0.000 claims abstract description 16
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 16
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 15
- 239000012634 fragment Substances 0.000 claims abstract description 11
- 241000700605 Viruses Species 0.000 claims abstract description 9
- 210000004369 blood Anatomy 0.000 claims abstract description 8
- 239000008280 blood Substances 0.000 claims abstract description 8
- 230000019491 signal transduction Effects 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 4
- 208000032839 leukemia Diseases 0.000 claims abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 4
- 206010025323 Lymphomas Diseases 0.000 claims abstract description 3
- 102100032937 CD40 ligand Human genes 0.000 claims description 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 9
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 6
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 6
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 6
- 230000003321 amplification Effects 0.000 claims description 5
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 5
- 210000004881 tumor cell Anatomy 0.000 claims description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 4
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 102100026882 Alpha-synuclein Human genes 0.000 claims description 3
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 3
- 102100027207 CD27 antigen Human genes 0.000 claims description 3
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 3
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 3
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 3
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims description 3
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 3
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 3
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 3
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 3
- 108091008874 T cell receptors Proteins 0.000 claims description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 3
- 230000022534 cell killing Effects 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 3
- 230000002068 genetic effect Effects 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims 1
- -1 β chain or ζ chain Proteins 0.000 claims 1
- 230000005909 tumor killing Effects 0.000 abstract description 6
- 238000010276 construction Methods 0.000 abstract description 4
- 230000007969 cellular immunity Effects 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
Abstract
The present invention relates to cellular immunity technical fields, and disclose a kind of Chimeric antigen receptor and application based on BMCA nano antibody sequence, it includes extracellular domain, transmembrane domain and primary signal transduction domain, and the extracellular domain includes the anti-BCMA antibody or its antigen-binding fragment of the alpaca of an alpaca BCMA polypeptide or multiple epitopes；For main application in tumor therapeutic agent, the tumour is the relevant tumor disease of blood, the relevant tumor disease of the blood be mainly include each quasi-leukemia and malignant lymphoma.The Chimeric antigen receptor and its application based on BMCA nano antibody sequence, expressed sequence is shorter, saves limited slow virus carrier space, and the Chimeric antigen receptor T cell specificity based on the antibody construction is more preferable, and tumor-killing ability is stronger.
Description
Technical field
The present invention relates to cellular immunity technical field, specially a kind of chimeric antigen based on BMCA nano antibody sequence by
Body and its application.
Background technique
In recent years, swollen based on Chimeric antigen receptor (chimeric angiten receptor, CAR) modification T cell
Tumor adoptive immunotherapy makes substantial progress.T cell after modification not only has a killing ability of targets neoplastic cells, and can gram
It takes tumor by local immunosupress microenvironment and breaks the state of host immune tolerance.CAR has been sent out at present by continuously improving
Forth generation is opened up.First generation CAR is mainly made of the scFv of identification tumor associated antigen and ITAM (usually CD3 ζ), still
Due to only having CD3 ζ activation signals, T cell cannot sufficiently rise in value, and the time-to-live is short in vivo for the T cell activated.The second generation
Costimulatory molecules such as CD28, CD134, CD137 etc. are added in CAR on the basis of generation CAR, enhance t cell activation,
Proliferation is held time in vivo, to improve antitumor effect.Third generation CAR be re-introduced on the basis of two generation CAR one with
On costimulatory molecules.Forth generation CAR (TRUCKS, T cells redirected for universal cytokine
Killing) main by introducing IL-12, the cell factors such as IL-23, IL-27 call together inherent immunity cell-macrophage etc. to kill
Hurt the tumour cell of TAA feminine gender.
Chimeric antigen receptor T cell is the means by gene modification, by an artificial synthesized CAR molecule
(Chimeric Antigen Receptor) is expressed on T cell film, identifies T cell simultaneously in such a way that antigen-antibody combines
Killing tumor cell.CAR molecule includes extracellular antigen binding regions, hinge area, transmembrane region and signal segment intracellular.Compare often
The CAR antigen binding regions seen are made of the scFv that the variable region of the heavy chain and light chain of people or mouse forms.Compared with ScFV,
Nano antibody sequence VHH expression cassette from alpaca is shorter, and specificity is higher.We are obtained by immune alpaca by screening
The BCMA nano antibody sequence affinity obtained is higher, and the Chimeric antigen receptor based on the sequence construct shows excellent in vitro
Tumor-killing vigor.
Summary of the invention
(1) the technical issues of solving
In view of the deficiencies of the prior art, the present invention provides a kind of Chimeric antigen receptors based on BMCA nano antibody sequence
And its application, it is shorter to have an expressed sequence, save limited slow virus carrier space, based on the chimeric antigen of the antibody construction by
The advantages that body T cell specificity is more preferable, and tumor-killing ability is stronger, solve common CAR antigen binding regions by people or
The longer problem low with tumor-killing ability of scFv expressed sequence of the variable region composition of the heavy chain and light chain of person mouse.
(2) technical solution
Quantitatively addition cement and sandstone and the purpose automatically added water, the present invention following technical side can be provided to realize
Case: a kind of Chimeric antigen receptor based on BMCA nano antibody sequence comprising extracellular domain, transmembrane domain and primary letter
Number transduction domain, the extracellular domain include the alpaca of an alpaca BCMA polypeptide or multiple epitopes anti-BCMA antibody or its
Antigen-binding fragment.
Preferably, one alpaca BCMA polypeptide or multiple epitopes alpaca anti-BCMA antibody or its antigen binding
Segment carries out periodically immune obtain to alpaca by Bacillus coli expression BCMA albumen.
Preferably, one alpaca BCMA polypeptide or multiple epitopes alpaca anti-BCMA antibody or its antigen binding
Segment is single domain antibody genetic fragment after transcription and amplification.
Preferably, the transmembrane domain is from being selected from following polypeptides: α chain, β chain or the ζ chain of T cell receptor, CD3 ε,
CD3ζ、CD4、CD5、CD8α、CD9、CD16、CD22、CD27、CD28、CD33、CD37、CD45、CD64、CD80、CD86、
CD134, CD137, CD152, CD154 and PD1.
Preferably, the transmembrane domain is from selected from following polypeptides: CD8 α, CD4, CD45, PD1 and CD154.
Preferably, the transmembrane domain is finally selected as CD154, is 1-54 amino acid sequence.
Preferably, primary signal transduction domain is from CD3 ζ or CD152 amino acid sequence.
Preferably, primary signal transduction domain is from CD8 α or CD152 amino acid sequence.
Preferably, the BCMA nano antibody sequence, sequence composition are as follows: DVQLQASGGGLVQAGGSLRLSCTASGR TFSTYFMAWFRQPPGKEREYVGGIRWSDGVPHYADSVKGRFTISRDNAKNTVYLQMNSLKSEDTAVYFCASRGIADG SDFGSYGQGTQVTVSS
Setting-out part is the core sequence of nano antibody.
A kind of application of the Chimeric antigen receptor based on BMCA nano antibody sequence, main application is in tumor therapeutic agent
In, the tumour is the relevant tumor disease of blood, the relevant tumor disease of the blood be mainly include each quasi-leukemia and
Malignant lymphoma.
Preferably, the Chimeric antigen receptor based on BMCA nano antibody sequence is in same tumor disease virus expression carrier
On, it packs tumour virus and infects T cell, patient's body is fed back to after amplification in vitro, realize and voluntarily stop immune detection point,
Special target cell killing tumour cell again.
(3) beneficial effect
Compared with prior art, the present invention provides a kind of Chimeric antigen receptor based on BMCA nano antibody sequence and its
Using, have it is following the utility model has the advantages that
The Chimeric antigen receptor based on BMCA nano antibody sequence, the nano antibody expressed sequence is shorter, saves limited
Slow virus carrier space, the Chimeric antigen receptor T cell specificity based on the antibody construction is more preferable, and tumor-killing ability is more
By force.
Specific embodiment
Below in conjunction with the embodiment in the present invention, technical solution in the embodiment of the present invention is carried out clearly and completely
Description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on this hair
Embodiment in bright, every other implementation obtained by those of ordinary skill in the art without making creative efforts
Example, shall fall within the protection scope of the present invention.
A kind of Chimeric antigen receptor based on BMCA nano antibody sequence comprising extracellular domain, transmembrane domain and
Primary signal transduce domain, extracellular domain include the alpaca of an alpaca BCMA polypeptide or multiple epitopes anti-BCMA antibody or
Its antigen-binding fragment.
The anti-BCMA antibody or its antigen-binding fragment of the alpaca of one alpaca BCMA polypeptide or multiple epitopes pass through big
Enterobacteria expresses BCMA albumen and carries out periodically immune obtain to alpaca.
The anti-BCMA antibody or its antigen-binding fragment of the alpaca of one alpaca BCMA polypeptide or multiple epitopes are by turning
It is single domain antibody genetic fragment after record and amplification.
Transmembrane domain is from being selected from following polypeptides: α chain, β chain or the ζ chain of T cell receptor, CD3 ε, CD3 ζ, CD4,
CD5、CD8α、CD9、CD16、CD22、CD27、CD28、CD33、CD37、CD45、CD64、CD80、CD86、CD134、CD137、
CD152, CD154 and PD1.
Transmembrane domain is from selected from following polypeptides: CD8 α, CD4, CD45, PD1 and CD154.
Transmembrane domain is finally selected as CD154, is 1-54 amino acid sequence.
Primary signal transduces domain from CD3 ζ or CD152 amino acid sequence.
Primary signal transduces domain from CD8 α or CD152 amino acid sequence.
The BCMA nano antibody sequence, sequence composition are as follows: DVQLQASGGGLVQAGGSLRLSCTASGRTFSTYFM
AWFRQPPGKEREYVGGIRWSDGVPHYADSVKGRFTISRDNAKNTVYLQMNSLKSEDTAVYFCASRGIADGSDFGSYG
QGTQVTVSS
Setting-out part is the core sequence of nano antibody.
A kind of application of the Chimeric antigen receptor based on BMCA nano antibody sequence, main application is in tumor therapeutic agent
In, tumour is the relevant tumor disease of blood, and the relevant tumor disease of blood is mainly including each quasi-leukemia and malignant lymphatic
Tumor.
For Chimeric antigen receptor based on BMCA nano antibody sequence on same tumor disease virus expression carrier, packaging is swollen
Tumor virus simultaneously infects T cell, and patient's body is fed back to after amplification in vitro, realizes and voluntarily stops immune detection point, and specific target
To cell killing tumour cell.
In conclusion it is somebody's turn to do Chimeric antigen receptor and its application based on BMCA nano antibody sequence, nano antibody expression
Sequence is shorter, saves limited slow virus carrier space, and the Chimeric antigen receptor T cell specificity based on the antibody construction is more
Good, tumor-killing ability is stronger.
It should be noted that term " includes " or any other variant thereof is intended to cover non-exclusive inclusion, thus
So that the process, method, article or equipment for including a series of elements not only includes those elements, but also including not clear
The other element listed, or further include for elements inherent to such a process, method, article, or device.Do not having more
In the case where more limitations, the element that is limited by sentence "including a ...", it is not excluded that including process, the side of the element
There is also other identical elements in method, article or equipment.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (11)
1. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence comprising extracellular domain, transmembrane domain and just
Grade signal transduction domain, the extracellular domain includes the anti-BCMA antibody of the alpaca of an alpaca BCMA polypeptide or multiple epitopes
Or its antigen-binding fragment.
2. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 1, it is characterised in that: institute
The anti-BCMA antibody or its antigen-binding fragment of state an alpaca BCMA polypeptide or multiple epitopes alpaca pass through Escherichia coli
Expression BCMA albumen carries out periodically immune obtain to alpaca.
3. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 2, it is characterised in that: institute
The anti-BCMA antibody or its antigen-binding fragment of state an alpaca BCMA polypeptide or multiple epitopes alpaca by transcription and expand
It is single domain antibody genetic fragment after increasing.
4. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 1, it is characterised in that: institute
Transmembrane domain is stated from selected from following polypeptides: the α chain of T cell receptor, β chain or ζ chain, CD3 ε, CD3 ζ, CD4, CD5, CD8
α、CD9、CD16、CD22、CD27、CD28、CD33、CD37、CD45、CD64、CD80、CD86、CD134、CD137、CD152、
CD154 and PD1.
5. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 4, it is characterised in that: institute
Transmembrane domain is stated from selected from following polypeptides: CD8 α, CD4, CD45, PD1 and CD154.
6. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 5, it is characterised in that: institute
It states transmembrane domain and is finally selected as CD154, be 1-54 amino acid sequence.
7. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 4, it is characterised in that: institute
Primary signal transduction domain is stated from CD3 ζ or CD152 amino acid sequence.
8. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 4, it is characterised in that: institute
Primary signal transduction domain is stated from CD8 α or CD152 amino acid sequence.
9. a kind of Chimeric antigen receptor based on BMCA nano antibody sequence described in -8 according to claim 1, it is characterised in that:
The BCMA nano antibody sequence, sequence composition are as follows: DVQLQASGGGLVQAGGSLRLSCTASGRTFSTYFMAWFRQPPG
KEREYVGGIRWSDGVPHYADSVKGRFTISRDNAKNTVYLQMNSLKSEDTAVYFCASRGIADGSDFGSYGQGTQVTVS
S
Setting-out part is the core sequence of nano antibody.
10. a kind of application of the Chimeric antigen receptor based on BMCA nano antibody sequence, which is characterized in that main application is swollen
In tumor therapeutic agent, the tumour is the relevant tumor disease of blood, and it includes each that the relevant tumor disease of the blood, which is main,
Quasi-leukemia and malignant lymphoma.
11. a kind of application of Chimeric antigen receptor based on BMCA nano antibody sequence according to claim 10, will weigh
Benefit requires any Chimeric antigen receptor based on BMCA nano antibody sequence of 1-8 to carry in same tumor disease expressing viral
It on body, packs tumour virus and infects T cell, patient's body is fed back to after amplification in vitro, realization voluntarily stops immune detection
Point, and special target cell killing tumour cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910042481.5A CN109694413A (en) | 2019-01-17 | 2019-01-17 | A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910042481.5A CN109694413A (en) | 2019-01-17 | 2019-01-17 | A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109694413A true CN109694413A (en) | 2019-04-30 |
Family
ID=66233975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910042481.5A Pending CN109694413A (en) | 2019-01-17 | 2019-01-17 | A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109694413A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111909271A (en) * | 2020-08-12 | 2020-11-10 | 深圳市茵冠生物科技有限公司 | BCMA chimeric antigen receptor based on single domain antibody and application thereof |
| CN111925451A (en) * | 2020-10-12 | 2020-11-13 | 北京广未生物科技有限公司 | BCMA (brain cell activating antigen) -targeted Chimeric Antigen Receptor (CAR) and application thereof |
| CN112028996A (en) * | 2020-10-30 | 2020-12-04 | 南京北恒生物科技有限公司 | Single domain antibodies targeting BCMA and uses thereof |
| WO2021063349A1 (en) * | 2019-09-30 | 2021-04-08 | 和铂医药(苏州)有限公司 | Antibody targeting bcma, bispecific antibody, and use thereof |
| CN114276452A (en) * | 2021-12-29 | 2022-04-05 | 源道隆（苏州）医学科技有限公司 | Nano antibody capable of being combined with BCMA (brain cell activating antigen) and application thereof |
| WO2022143611A1 (en) * | 2020-12-29 | 2022-07-07 | 宁波茂行生物医药科技有限公司 | Bcma-targeting single-domain antibody |
| EP3845244A4 (en) * | 2018-08-24 | 2022-09-07 | Shenzhen Pregene Biopharma Co. Ltd. | Anti-bcma single domain antibodies and application thereof |
| WO2023044991A1 (en) * | 2021-09-24 | 2023-03-30 | 四川大学 | Antibody specifically targeting tumor epcam antigen and application thereof |
| CN117186229A (en) * | 2022-12-06 | 2023-12-08 | 成都赛恩吉诺生物科技有限公司 | Anti-human BCMA nanobody with long CDR3 sequence, CAR-T and application |
| CN117430709A (en) * | 2023-12-21 | 2024-01-23 | 康维众和(中山)生物药业有限公司 | Nanometer antibody and application thereof |
-
2019
- 2019-01-17 CN CN201910042481.5A patent/CN109694413A/en active Pending
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3845244A4 (en) * | 2018-08-24 | 2022-09-07 | Shenzhen Pregene Biopharma Co. Ltd. | Anti-bcma single domain antibodies and application thereof |
| WO2021063349A1 (en) * | 2019-09-30 | 2021-04-08 | 和铂医药(苏州)有限公司 | Antibody targeting bcma, bispecific antibody, and use thereof |
| WO2022033057A1 (en) * | 2020-08-12 | 2022-02-17 | 深圳市茵冠生物科技有限公司 | Single-domain antibody-based bcma chimeric antigen receptor, and application thereof |
| CN111909271A (en) * | 2020-08-12 | 2020-11-10 | 深圳市茵冠生物科技有限公司 | BCMA chimeric antigen receptor based on single domain antibody and application thereof |
| CN111925451B (en) * | 2020-10-12 | 2021-01-29 | 佑仁细胞工程(浙江)有限公司 | BCMA (brain cell activating antigen) -targeted Chimeric Antigen Receptor (CAR) and application thereof |
| CN111925451A (en) * | 2020-10-12 | 2020-11-13 | 北京广未生物科技有限公司 | BCMA (brain cell activating antigen) -targeted Chimeric Antigen Receptor (CAR) and application thereof |
| CN112028996B (en) * | 2020-10-30 | 2021-01-22 | 南京北恒生物科技有限公司 | Single domain antibodies targeting BCMA and uses thereof |
| CN112028996A (en) * | 2020-10-30 | 2020-12-04 | 南京北恒生物科技有限公司 | Single domain antibodies targeting BCMA and uses thereof |
| WO2022143611A1 (en) * | 2020-12-29 | 2022-07-07 | 宁波茂行生物医药科技有限公司 | Bcma-targeting single-domain antibody |
| WO2023044991A1 (en) * | 2021-09-24 | 2023-03-30 | 四川大学 | Antibody specifically targeting tumor epcam antigen and application thereof |
| CN114276452A (en) * | 2021-12-29 | 2022-04-05 | 源道隆（苏州）医学科技有限公司 | Nano antibody capable of being combined with BCMA (brain cell activating antigen) and application thereof |
| CN117186229A (en) * | 2022-12-06 | 2023-12-08 | 成都赛恩吉诺生物科技有限公司 | Anti-human BCMA nanobody with long CDR3 sequence, CAR-T and application |
| CN117186229B (en) * | 2022-12-06 | 2024-03-29 | 成都赛恩吉诺生物科技有限公司 | Anti-human BCMA nanobody with long CDR3 sequence, CAR-T and application |
| CN117430709A (en) * | 2023-12-21 | 2024-01-23 | 康维众和(中山)生物药业有限公司 | Nanometer antibody and application thereof |
| CN117430709B (en) * | 2023-12-21 | 2024-03-26 | 康维众和(中山)生物药业有限公司 | Nanometer antibody and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109694413A (en) | A kind of Chimeric antigen receptor and its application based on BMCA nano antibody sequence | |
| CN106414748B (en) | Chimeric antigen receptor and method of preparation | |
| CN106687584B (en) | Soluble antibody complexes for T cell or NK cell activation and expansion | |
| WO2018121712A1 (en) | Novel chimeric antigen receptor and use thereof | |
| JP2018529327A (en) | Immune effector cells targeting anti-mesothelin fully human antibodies and mesothelin | |
| CN109735500B (en) | Secretory CD 133-targeted CAR-T cell and preparation method and application thereof | |
| JP2024045111A (en) | Methods for producing and using guidance and navigation control proteins | |
| JP2018534928A (en) | Methods, kits, agents and devices for transduction | |
| US20220306723A1 (en) | Chimeric antigen receptor comprising cd40 cytoplasmic domain and uses thereof | |
| CN108752482A (en) | Carry Chimeric antigen receptor and its application of truncation or not truncated myeloid cell triggering property receptor signal structure | |
| Radichev et al. | Towards antigen-specific Tregs for type 1 diabetes: Construction and functional assessment of pancreatic endocrine marker, HPi2-based chimeric antigen receptor | |
| Tal et al. | An NCR1-based chimeric receptor endows T-cells with multiple anti-tumor specificities | |
| CN108265027B (en) | Tumor specific T cell based on non-natural glycometabolism engineering and construction method thereof | |
| Fu et al. | CD4+ T cells engineered with FVIII-CAR and murine Foxp3 suppress anti-factor VIII immune responses in hemophilia a mice | |
| WO2021202863A1 (en) | Human ror-1 antibody and anti-ror-1-car-t cells | |
| CN108822216B (en) | Carry the Chimeric antigen receptor and its application of truncation or not truncated nature cell toxin receptor signal structure | |
| WO2018103734A1 (en) | Chimeric antigen receptor and use thereof and preparation method therefor | |
| US20210275588A1 (en) | Biomolecule Coated Particles and Films and Uses Thereof | |
| Kusabuka et al. | Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy | |
| Jafarzadeh et al. | Construction and functional characterization of a fully human anti-mesothelin chimeric antigen receptor (CAR) expressing T cell | |
| JP2024504162A (en) | Bispecific chimeric antigen receptor that binds CD19 and CD22 | |
| WO2024094004A1 (en) | Fully human antibody targeting cd123 and use thereof | |
| WO2023044991A1 (en) | Antibody specifically targeting tumor epcam antigen and application thereof | |
| US11976297B2 (en) | Engineered immune cells with receptor cross-talk | |
| Lian et al. | A novel multimeric sCD19‐streptavidin fusion protein for functional detection and selective expansion of CD19‐targeted CAR‐T cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190430 |
|
| WD01 | Invention patent application deemed withdrawn after publication |