CN114381432A - Humanized mouse tumor cell model construction method - Google Patents
Humanized mouse tumor cell model construction method Download PDFInfo
- Publication number
- CN114381432A CN114381432A CN202011128433.7A CN202011128433A CN114381432A CN 114381432 A CN114381432 A CN 114381432A CN 202011128433 A CN202011128433 A CN 202011128433A CN 114381432 A CN114381432 A CN 114381432A
- Authority
- CN
- China
- Prior art keywords
- mouse
- humanized
- tumor
- cell model
- tumor cell
- 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
- 210000004881 tumor cell Anatomy 0.000 title claims abstract description 30
- 238000011577 humanized mouse model Methods 0.000 title claims abstract description 21
- 238000010276 construction Methods 0.000 title claims abstract description 11
- 210000004027 cell Anatomy 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 19
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 12
- 238000010172 mouse model Methods 0.000 claims description 11
- 241000699670 Mus sp. Species 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 230000000259 anti-tumor effect Effects 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 6
- 231100000027 toxicology Toxicity 0.000 claims description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 238000004806 packaging method and process Methods 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- 238000012216 screening Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 238000011081 inoculation Methods 0.000 claims 2
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 abstract description 6
- 108091008036 Immune checkpoint proteins Proteins 0.000 abstract description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 abstract description 2
- 241001529936 Murinae Species 0.000 abstract description 2
- 230000006399 behavior Effects 0.000 abstract description 2
- 229940125644 antibody drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
Images
Classifications
-
- 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
- C12N5/0693—Tumour cells; Cancer cells
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- 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
- C12N2503/00—Use of cells in diagnostics
- C12N2503/02—Drug screening
-
- 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
- C12N2510/00—Genetically modified cells
-
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/106—Plasmid DNA for vertebrates
- C12N2800/107—Plasmid DNA for vertebrates for mammalian
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Plant Pathology (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses a humanized mouse tumor cell model construction method, which belongs to the technical field of cell model construction. The humanized mouse tumor cell model which is successfully manufactured is provided with human extracellular regions, so that human immune checkpoint drugs can be screened, and the murine intracellular regions ensure that intracellular signal conduction is not influenced and external stimuli are faithfully converted into intracellular behaviors.
Description
Technical Field
The invention belongs to the technical field of cell model construction, and particularly relates to a humanized mouse tumor cell model construction method.
Background
The humanized mouse model is a mouse model with functional human genes, cells or tissues, and is a chimera formed by transplanting human cells or tissues and a mouse.
There is a continuing need for new "humanized" mouse models that allow robust engraftment of human hematopoietic stem cells with human patient-derived tumor xenografts and/or human tumor cell lines to enable studies of the interaction between the human immune system and human cancer to be conducted in vivo.
Disclosure of Invention
1. Technical problem to be solved by the invention
The invention aims to solve the defect of high failure rate of humanized mice in the prior art.
2. Technical scheme
In order to achieve the purpose, the technical scheme provided by the invention is as follows:
the invention relates to a humanized mouse tumor cell model construction method, which comprises the following steps:
s1, selecting an NSG type mouse;
s2, determining a human sequence, and synchronously determining a humanized replacement region of the human sequence in the mouse;
s3, designing sgRNG against mouse cell model sequences in the humanized replacement region;
s4, designing and constructing a humanized vector according to the obtained sgRGRN;
s5, introducing the humanized vector into mouse cells, and performing directional treatment on the mouse cells to obtain vector cells;
s6, packaging and infecting the cells of the mouse through the virus, so that the humanized sequence is contained in the expression of the mouse cell model to obtain the tumor cell mouse model.
Preferably, the mouse model for NSG in S1 is a h-PBMC-NSG mouse.
Preferably, the NSG mouse model comprises a control group of CD34+ mice.
Preferably, the mice are selected to be 2x10, 6 cells/mouse at the lowest, and are inoculated subcutaneously.
Preferably, a normal control group is established in the construction method, and the normal control group mice are inoculated by selecting normal mice.
Preferably, the method is applied to evaluating the effectiveness of the targeted drug, screening and developing the targeted drug, evaluating the anti-tumor effect of the targeted drug in combination with other drugs, or researching the toxicology of the targeted drug.
Preferably, a human tumor cell is administered to the genetically modified immunodeficient mouse, wherein the human tumor cell forms a solid or non-solid tumor in the genetically modified immunodeficient mouse; administering a test substance to the genetically modified immunodeficient mouse; and determining the response of said solid or non-solid tumor to said test agent, wherein an inhibitory effect of said test agent on said tumor and/or tumor cells identifies said test agent as having anti-tumor activity.
3. Advantageous effects
Compared with the prior art, the technical scheme provided by the invention has the following beneficial effects:
the humanized mouse tumor cell constructed by the method replaces the extracellular region of the mouse gene with the human sequence, and the intracellular region retains the complete mouse sequence. The humanized mouse tumor cell model which is successfully prepared is provided with an humanized extracellular region, and humanized immune checkpoint drugs (such as antibody drugs; CAR T, CAR NK and the like) can be screened; the murine intracellular domain ensures that intracellular signal transduction is not affected, and external stimuli are faithfully transformed into intracellular behaviors (activation or inhibition).
The humanized mouse can be used for evaluating the drug effect of the antibody tumor and has important guiding significance on the clinical effect of drug development. Meanwhile, the method is an ideal model for evaluating the safety of the anti-human antibody medicament, and clinical in-vivo evaluation of the toxicology of the antibody medicament is carried out.
The humanized mouse can be used for single-drug evaluation of an anti-human antibody, can also be used for evaluating the anti-tumor effect of the antibody combined with other drugs (small molecules or antibody drugs) and evaluating the killing tumor of CAR T and CAR NK cells, and has profound guiding significance for evaluating the effect of a clinical prodrug.
Drawings
FIG. 1 is a flow chart of a method for constructing a humanized mouse tumor cell model according to the present invention.
Detailed Description
In order to facilitate an understanding of the invention, the invention will now be described more fully hereinafter with reference to the accompanying drawings, in which several embodiments of the invention are shown, but which may be embodied in many different forms and are not limited to the embodiments described herein, but rather are provided for the purpose of providing a more thorough disclosure of the invention.
It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present; when an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present; the terms "vertical," "horizontal," "left," "right," and the like as used herein are for illustrative purposes only.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs; the terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention; as used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
Example 1
Referring to fig. 1, the method for constructing a humanized mouse tumor cell model of this embodiment includes the following steps:
s1, selecting an NSG type mouse;
s2, determining a human sequence, and synchronously determining a humanized replacement region of the human sequence in the mouse;
s3, designing sgRNG against mouse cell model sequences in the humanized replacement region;
s4, designing and constructing a humanized vector according to the obtained sgRGRN;
s5, introducing the humanized vector into mouse cells, and performing directional treatment on the mouse cells to obtain vector cells;
s6, packaging and infecting the cells of the mouse through the virus, so that the humanized sequence is contained in the expression of the mouse cell model to obtain the tumor cell mouse model.
The mouse model for NSG in S1 of this example was a h-PBMC-NSG mouse.
The NSG mouse model of this example comprises a control group of CD34+ mice.
The mice of this example were selected at a minimum of 2x10, 6 cells/mouse, and were inoculated subcutaneously.
In the construction method of this embodiment, a normal control group is established, and the normal control group mice are inoculated with a selected normal mouse.
The method of the embodiment is applied to evaluating the effectiveness of the targeted drug, screening and developing the targeted drug, evaluating the anti-tumor effect of the targeted drug in combination with other drugs, or researching the toxicology of the targeted drug.
Administering a human tumor cell of the present embodiment to the genetically modified immunodeficient mouse, wherein the human tumor cell forms a solid or non-solid tumor in the genetically modified immunodeficient mouse; administering a test substance to the genetically modified immunodeficient mouse; and determining the response of said solid or non-solid tumor to said test agent, wherein an inhibitory effect of said test agent on said tumor and/or tumor cells identifies said test agent as having anti-tumor activity.
The above-mentioned embodiments only express a certain implementation mode of the present invention, and the description thereof is specific and detailed, but not construed as limiting the scope of the present invention; it should be noted that, for those skilled in the art, without departing from the concept of the present invention, several variations and modifications can be made, which are within the protection scope of the present invention; therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (7)
1. A humanized mouse tumor cell model construction method is characterized in that: the method comprises the following steps:
s1, selecting an NSG type mouse;
s2, determining a human sequence, and synchronously determining a humanized replacement region of the human sequence in the mouse;
s3, designing sgRNG against mouse cell model sequences in the humanized replacement region;
s4, designing and constructing a humanized vector according to the obtained sgRGRN;
s5, introducing the humanized vector into mouse cells, and performing directional treatment on the mouse cells to obtain vector cells;
s6, packaging and infecting the cells of the mouse through the virus, so that the humanized sequence is contained in the expression of the mouse cell model to obtain the tumor cell mouse model.
2. The method for constructing a humanized mouse tumor cell model according to claim 1, wherein the method comprises the following steps: the mouse model for NSG in S1 is a h-PBMC-NSG mouse.
3. The method for constructing a humanized mouse tumor cell model according to claim 2, wherein the method comprises the following steps: the NSG mouse model included a control group of CD34+ mice.
4. The method for constructing a humanized mouse tumor cell model according to claim 1, wherein the method comprises the following steps: the mouse is selected to be 2x10 and 6 cells/mouse at the lowest, and subcutaneous inoculation is adopted.
5. The method for constructing a humanized mouse tumor cell model according to claim 1, wherein the method comprises the following steps: in the construction method, a normal control group is established, and normal mice are selected from the mice of the normal control group for inoculation.
6. The method for constructing a humanized mouse tumor cell model according to any one of claims 1 to 5, wherein: the method is applied to evaluating the effectiveness of the targeted drug, screening and developing the targeted drug, evaluating the anti-tumor effect of the targeted drug in combination with other drugs, or researching the toxicology of the targeted drug.
7. The method for constructing a humanized mouse tumor cell model according to claim 1, wherein the method comprises the following steps: administering human tumor cells to the genetically modified immunodeficient mouse, wherein the human tumor cells form a solid or non-solid tumor in the genetically modified immunodeficient mouse; administering a test substance to the genetically modified immunodeficient mouse; and determining the response of said solid or non-solid tumor to said test agent, wherein an inhibitory effect of said test agent on said tumor and/or tumor cells identifies said test agent as having anti-tumor activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011128433.7A CN114381432A (en) | 2020-10-20 | 2020-10-20 | Humanized mouse tumor cell model construction method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011128433.7A CN114381432A (en) | 2020-10-20 | 2020-10-20 | Humanized mouse tumor cell model construction method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114381432A true CN114381432A (en) | 2022-04-22 |
Family
ID=81193169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011128433.7A Pending CN114381432A (en) | 2020-10-20 | 2020-10-20 | Humanized mouse tumor cell model construction method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114381432A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109266656A (en) * | 2018-10-10 | 2019-01-25 | 江苏集萃药康生物科技有限公司 | A kind of construction method of PD1 humanization BALB/c mouse model and its application |
| CN109929875A (en) * | 2019-03-12 | 2019-06-25 | 江苏集萃药康生物科技有限公司 | A kind of construction method of LAG3 gene humanized animal's model and its application |
| CN111019972A (en) * | 2019-12-30 | 2020-04-17 | 江苏集萃药康生物科技有限公司 | Construction method and application of CD27 humanized mouse model |
| CN111088287A (en) * | 2019-12-20 | 2020-05-01 | 江苏浦珠生物医药科技有限公司 | HER2 gene humanized mouse tumor cell model, construction method and application |
| CN111254120A (en) * | 2019-12-20 | 2020-06-09 | 江苏浦珠生物医药科技有限公司 | EpCAM gene humanized mouse tumor cell model, construction method and application |
| CN111621523A (en) * | 2020-06-09 | 2020-09-04 | 湖南昭泰生物医药有限公司 | ACE2 cell humanized mouse model and construction method and application thereof |
| CN111647623A (en) * | 2020-07-14 | 2020-09-11 | 江苏集萃药康生物科技有限公司 | Construction method and application of SIRPA humanized animal model |
-
2020
- 2020-10-20 CN CN202011128433.7A patent/CN114381432A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109266656A (en) * | 2018-10-10 | 2019-01-25 | 江苏集萃药康生物科技有限公司 | A kind of construction method of PD1 humanization BALB/c mouse model and its application |
| CN109929875A (en) * | 2019-03-12 | 2019-06-25 | 江苏集萃药康生物科技有限公司 | A kind of construction method of LAG3 gene humanized animal's model and its application |
| CN111088287A (en) * | 2019-12-20 | 2020-05-01 | 江苏浦珠生物医药科技有限公司 | HER2 gene humanized mouse tumor cell model, construction method and application |
| CN111254120A (en) * | 2019-12-20 | 2020-06-09 | 江苏浦珠生物医药科技有限公司 | EpCAM gene humanized mouse tumor cell model, construction method and application |
| CN111019972A (en) * | 2019-12-30 | 2020-04-17 | 江苏集萃药康生物科技有限公司 | Construction method and application of CD27 humanized mouse model |
| CN111621523A (en) * | 2020-06-09 | 2020-09-04 | 湖南昭泰生物医药有限公司 | ACE2 cell humanized mouse model and construction method and application thereof |
| CN111647623A (en) * | 2020-07-14 | 2020-09-11 | 江苏集萃药康生物科技有限公司 | Construction method and application of SIRPA humanized animal model |
Non-Patent Citations (2)
| Title |
|---|
| YIN,L.等: "Humanized mouse model:a review on preclinical application for cancer immunotherapy", AMERICAN JOURNAL OF CANCER RESEARCH * |
| 郭文文等: "免疫系统人源化小鼠模型的构建及其在肿瘤治疗研究中的应用", 《中国比较医学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Querdel et al. | Human engineered heart tissue patches remuscularize the injured heart in a dose-dependent manner | |
| Ghahremani et al. | Frontoparietal functional connectivity in the common marmoset | |
| CN104781278B (en) | For the antibody of TAU | |
| Rancz et al. | Widespread vestibular activation of the rodent cortex | |
| Lahoud et al. | Oxytocinergic manipulations in corticolimbic circuit differentially affect fear acquisition and extinction | |
| CN102639565B (en) | IL1RAP expression on acute and chronic myeloid leukemia cells | |
| Giordano et al. | From combinatorial peptide selection to drug prototype (I): targeting the vascular endothelial growth factor receptor pathway | |
| JP7339990B2 (en) | Methods for improving cell therapy | |
| UA118749C2 (en) | Antibody constructs for cdh19 and cd3 | |
| UA125962C2 (en) | Bispecific antibodies specific for a costimulatory tnf receptor | |
| CN107007833A (en) | Anti- IL 36R antibody | |
| CN108779160A (en) | Using engineering T cell to treat the cancer in central nervous system | |
| Maresca et al. | Acoustic biomolecules enhance hemodynamic functional ultrasound imaging of neural activity | |
| Benjamin et al. | Intravital imaging of metastasis in adult Zebrafish | |
| CN106255702A (en) | The therapy to transthyretin (TTR) amyloidosis based on antibody and human antibody thereof | |
| CN107207591A (en) | Blood-brain barrier receptor antibody and application method | |
| CN101563105A (en) | Compositions and methods for inhibiting growth of smad4-deficient cancers | |
| Wicker et al. | Descending projections from the substantia nigra pars reticulata differentially control seizures | |
| UA124269C2 (en) | Uses of il-13 antagonists for treating atopic dermatitis | |
| Trujillo-Pisanty et al. | Dopamine neurons do not constitute an obligatory stage in the final common path for the evaluation and pursuit of brain stimulation reward | |
| Ammann et al. | The motor cortex is involved in the generation of classically conditioned eyelid responses in behaving rabbits | |
| Ego-Stengel et al. | Coding of apparent motion in the thalamic nucleus of the rat vibrissal somatosensory system | |
| Sta Maria et al. | Spatio-temporal biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells by PET imaging in a preclinical tumor model | |
| CN107108718A (en) | Technology and its application of soluble general enhancing ADCC synthesis fusion and fusogenic peptide | |
| CN114381432A (en) | Humanized mouse tumor cell model construction method |
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: 20220422 |
|
| WD01 | Invention patent application deemed withdrawn after publication |