CN116211860B - Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination - Google Patents
Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination Download PDFInfo
- Publication number
- CN116211860B CN116211860B CN202310520332.1A CN202310520332A CN116211860B CN 116211860 B CN116211860 B CN 116211860B CN 202310520332 A CN202310520332 A CN 202310520332A CN 116211860 B CN116211860 B CN 116211860B
- Authority
- CN
- China
- Prior art keywords
- inhibitor
- application
- tumor
- cells
- medicines
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 23
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 229940079593 drug Drugs 0.000 title claims abstract description 14
- 229940122360 Casein kinase 2 inhibitor Drugs 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 210000002865 immune cell Anatomy 0.000 title abstract description 8
- 239000003112 inhibitor Substances 0.000 title abstract description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 29
- 230000000779 depleting effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 238000009169 immunotherapy Methods 0.000 abstract description 5
- 238000002648 combination therapy Methods 0.000 abstract description 2
- 210000003162 effector t lymphocyte Anatomy 0.000 abstract description 2
- 230000003915 cell function Effects 0.000 description 7
- 238000003501 co-culture Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 102000052052 Casein Kinase II Human genes 0.000 description 4
- 108010010919 Casein Kinase II Proteins 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 102000043139 CK2 family Human genes 0.000 description 3
- 229920001917 Ficoll Polymers 0.000 description 3
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 3
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 239000000833 heterodimer Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101150063370 Gzmb gene Proteins 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 108010025076 Holoenzymes Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 229940126530 T cell activator Drugs 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- SLPJGDQJLTYWCI-UHFFFAOYSA-N dimethyl-(4,5,6,7-tetrabromo-1h-benzoimidazol-2-yl)-amine Chemical compound BrC1=C(Br)C(Br)=C2NC(N(C)C)=NC2=C1Br SLPJGDQJLTYWCI-UHFFFAOYSA-N 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
Abstract
The application belongs to the field of biological medicines, and relates to application of a CK2 inhibitor CX4945 in preparation of medicines, inhibitors and combinations for preventing immune cells from being exhausted in tumor treatment, and the CK2 inhibitor provided by the application can effectively improve the condition of exhausting effector T cells in tumor tissues and enhance the treatment effect of anti-PD-1 medicines. The medicine has no obvious side effect, can be prepared into tumor immunotherapy medicine, and provides a new combined therapy mode. The medicine can be prepared into oral medicine, is convenient to treat, and has high patient compliance.
Description
Technical Field
The application belongs to the field of biological medicine, and relates to an application of a CK2 inhibitor CX4945 in preparing medicines for preventing immune cell depletion in tumor treatment, an inhibitor and a combination.
Background
Malignant tumor is a progressive disease in which normal cells proliferate and differentiate abnormally and are uncontrolled. At present, the morbidity and mortality of malignant tumors continuously rise, a large number of patients with advanced tumors need to take medicines for a long time, and the conventional treatment has high medicine resistance and poor prognosis. At present, immunotherapy is widely applied in the field of tumors as an emerging tumor treatment mode, wherein anti-PD-1/PD-L1 drugs are outstanding in inhibiting tumor growth and improving tumor immune microenvironment. However, the anti-PD-1 drugs are often used in clinical applications to further exacerbate the patient's condition due to their low effectiveness and resistance.
Protein Kinase CK2, also known as Casein Kinase 2 (Casein Kinase ii), is a ubiquitous protein Kinase that regulates metabolic pathways, signal transduction, transcription, translation and replication. The enzyme is a tetrameric holoenzyme consisting of three subunits, α, α' and β. The alpha and alpha' subunits have a catalytic effect and the beta subunit has a regulatory effect. Enzymes are localized in the endoplasmic reticulum and golgi apparatus. Previous studies have shown that CK2 is involved in differentiation of Th17 and Treg cells, but the effect of CK2 on immune cell function, particularly on T cell depletion function, in tumor tissues has not been verified or solved by the ability to achieve an effect of enhancing immunotherapy through modulation of protein kinase CK 2.
Disclosure of Invention
The application mainly aims at providing a regulatory protein kinase CK2 for realizing the purpose of regulating tumor immunotherapy.
In order to achieve the above object, according to one aspect of the present application, there is provided the use of CK2 inhibitor CX4945 for the preparation of a medicament for preventing immune cell depletion in tumor therapy.
The application also provides an inhibitor for preventing immune cell depletion in tumor treatment, wherein the inhibitor comprises a CK2 inhibitor.
The inhibitor provided according to the present application is CX4945.
The application also provides a combination for preventing immune cell depletion in tumor treatment, wherein the combination comprises an anti-PD-1 antibody and a CK2 inhibitor CX4945.
The beneficial effects of the application are as follows:
the CK2 inhibitor can effectively improve the depletion condition of effector T cells in tumor tissues, and simultaneously enhance the treatment effect of the anti-PD-1 medicament. The medicine has no obvious side effect, can be prepared into tumor immunotherapy medicine, and provides a new combined therapy mode. The medicine can be prepared into oral medicine, is convenient to treat, and has high patient compliance.
Drawings
The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this specification, illustrate embodiments of the application and together with the description serve to explain the application. In the drawings:
FIG. 1 shows the in vitro heterodimer induced CD8 of the present application + Flow cytometry of T cell depletion.
FIG. 2 shows CX4945 inhibiting CD8 + Flow cytometry of T cell depletion.
FIG. 3 shows that CX4945 in combination with anti-PD-1 of the application effectively enhances CD8 + The mean fluorescence intensity of granorubicin B for T cell function (co-culture with tumor cells).
FIG. 4 shows that CX4945 in combination with anti-PD-1 of the application effectively enhances CD8 + Statistical plots of granorubin B for T cell function (co-culture with tumor cells).
FIG. 5 shows that CX4945 in combination with anti-PD-1 of the application effectively enhances CD8 + The mean fluorescence intensity of interferon gamma for T cell function (co-culture with tumor cells).
FIG. 6 shows that CX4945 in combination with anti-PD-1 of the application effectively enhances CD8 + Statistical plots of interferon gamma for T cell function (co-culture with tumor cells).
FIG. 7 shows that CX4945 in combination with anti-PD-1 of the application effectively enhances CD8 + Flow cytometry of T cell function (co-culture with tumor cells).
FIG. 8 is a schematic representation of CX4945 in combination with anti-PD-1 in the treatment of lung adenocarcinoma in mice according to the application.
Figure 9 is a statistical plot of the effective tumor weight inhibition of the CX4945 combination anti-PD-1 treatment of the application.
FIG. 10 is a graph showing that CX4945 in combination with anti-PD-1 treatment of the application is effective in inhibiting tumor growth.
FIG. 11 CX4945 in vivo according to the application is effective in promoting CD8 + T cell infiltrating CD8 + T cell duty cycle plot.
Detailed Description
The application is described in further detail below with reference to the drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the application and are not limiting thereof. It should be further noted that, for convenience of description, only some, but not all experimental results related to the present application are shown in the drawings.
Example 1 in vitro CD8 + And (6) constructing a T cell depletion model.
1. Peripheral blood mononuclear cell extraction:
(1) Peripheral blood of healthy volunteers was added to a 15 mL centrifuge tube, diluted with PBS (buffer), and diluted in equal volume;
(2) Ficoll: the above diluent=1:1 or 1:2, and the diluent is slowly added into Ficoll (separating liquid of specific density cells) along the pipe wall to form a dividing surface, which cannot be uniformly mixed;
(3) Centrifuging at 1800 rpm for 18 min, quickly rising and slowly falling, and reducing the speed to zero;
(4) Aspirating the buffy coat (PBMC layer, peripheral blood mononuclear cell layer) (between yellow serum layer and Ficoll fluid) with a sterile pipette;
(5) The aspirated buffy coat was centrifuged and the supernatant was discarded and washed once with PBS to obtain PBMCs (peripheral blood mononuclear cells).
2. CD8 + Construction of a T cell depletion model:
(1) Separation of CD8 from PBMC Using magnetic beads + T CELLs stimulated with 25. Mu.L/mL of STEM CELL, inc. T CELL activator to activate CD8 + T cells (containing IL-2 (10 ng/mL) in the medium) were maintained expanded with IL-2 for 3 days after incubation until day 7.
(2) Heterodimers were prepared and antibodies to rat anti-human CD3 and goat anti-rat IgG were mixed in a molar ratio of 2:1.
(3) Adding the prepared heterodimer into a culture medium (containing 10ng/mL IL-2) to induce CD8 + T cells were depleted for two days to obtain CD8 + T cells.
Results:
as shown in FIG. 1, PD-1 increased with the heterodimer concentration in the culture system + Tim-3 + CD8 + The proportion of T cells is also gradually increased, suggesting that heterodimers can significantly promote CD8 + Depletion of T cells.
As shown in fig. 2: CX4945 for CD8 under normal culture conditions + The proportional effect of T cells is not apparent. While in the induction of depletion of CD8 + CX4945 can obviously inhibit PD-1 in a T cell model + Tim-3 + T cell ratio and promote PD-1 - Tim-3 - The ratio of T increases, p value<0.05 p value<0.01 p value<0.001 p value<0.0001. Suggesting that CX4945 may inhibit CD8 + Depletion of T cells.
Example 2 in vitro CD8 + Co-culture of T cells and tumor cells
A549 cells (lung cancer human alveolar basal epithelial cells) were cultured and expanded in vitro using 1640 medium containing 10% fbs and 1% diabody;
when the confluence of A549 reaches 70%, performing digestion counting;
CD8 to induce depletion + T cells and tumor cells were co-cultured in a 1 to 1 ratio, and PBS, CX4945 (10. Mu.M) or anti-PD-1 (20. Mu.g/mL) was added during co-culture to treat.
Results:
as shown in fig. 3, 4, 5, and 6, anti-PD-1 in combination with CX4945 further enhanced CD8 depletion compared to the single drug group + Capacity of T cells to produce IFN- γ (interferon γ) and granzyme (GzmB) (granamycin B), p value<0.05 p value<0.01 p value<0.001 p value<0.0001; as shown in fig. 7, 8, anti-PD-1 in combination with CX4945 further restored CD8 depletion compared to the single drug group + Functional cell populations of T cells (i.e., IFN-r - GzmB - T cell populations were significantly reduced). The results suggest that CX4945 combined with anti-PD-1 can effectively improve the depletion of CD8 + T cell function.
Example 3 in vivo CX4945 in combination with anti-PD-1 treatment of lung adenocarcinoma in mice.
Construction of tumor-bearing mice:
(1) Female C57BL/6 mice of 5-6 weeks of age were used for the construction of tumor-bearing models:
(2) Lewis cells after digestion and counting were according to 1X10 6 mu.L/100. Mu.L was inoculated subcutaneously into mice;
(3) The size of the tumor to be transplanted is as long as 100 mm 3 Grouping treatment is carried out left and right;
(4) A total of four groups of 6 mice, PBS group, CX4945 group (100 mg/kg once a day), anti-PD-1 group (150. Mu.g/dose twice a week) and combination treatment group were treated accordingly as in FIG. 8.
Results:
as shown in fig. 9 and 10, the anti-PD-1 combined CX4945 significantly inhibited the increase in tumor volume, increased weight, and did not cause significant side effects compared to the single drug group, and the effective rate reached 83.3% (5/6).
As shown in fig. 11, anti-PD-1 in combination with CX4945 significantly promoted CD8 compared to the single drug group + Infiltration of T cells. The result suggests that CX4945 combined with anti-PD-1 can effectively enhance the therapeutic effect of anti-PD-1.
The disclosed embodiments of the application are described in detail herein using a number of examples, but are not to be construed as limiting the application. It should also be noted that although preferred embodiments have been described in detail herein, it should be emphasized that the present application is not limited to these specific embodiments. Indeed, any obvious modification, equivalent replacement or other improvement made by those skilled in the art without departing from the inventive concept shall fall within the scope of the present application.
Claims (1)
1. Combination of CK2 inhibitor CX4945 and anti-PD-1 antibody for preventing CD8 in preparation of tumor treatment + Use of a T cell depleting drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310520332.1A CN116211860B (en) | 2023-05-10 | 2023-05-10 | Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310520332.1A CN116211860B (en) | 2023-05-10 | 2023-05-10 | Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116211860A CN116211860A (en) | 2023-06-06 |
| CN116211860B true CN116211860B (en) | 2023-08-22 |
Family
ID=86571679
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310520332.1A Active CN116211860B (en) | 2023-05-10 | 2023-05-10 | Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116211860B (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105560239A (en) * | 2015-12-30 | 2016-05-11 | 耿炜 | Use of CX4945 for preparation of drug having reversal effect on gastric cancer cisplatin-resistant radiation tolerance |
| WO2017070137A1 (en) * | 2015-10-20 | 2017-04-27 | Bristol-Myers Squibb Company | Combination of ck2 inhibitors and immune checkpoint modulators for cancer treatment |
| TW201737940A (en) * | 2016-04-08 | 2017-11-01 | 基利科學股份有限公司 | Compositions and methods for treating cancer, inflammatory diseases and autoimmune diseases |
| CN112274642A (en) * | 2020-10-15 | 2021-01-29 | 北京大学人民医院 | Application of CK2 inhibitor in preparation of medicine for treating rheumatoid arthritis |
| CN112789292A (en) * | 2018-07-31 | 2021-05-11 | 皮里斯制药有限公司 | Novel fusion proteins specific for CD137 and PD-L1 |
| CN113015529A (en) * | 2018-10-19 | 2021-06-22 | 生华生物科技股份有限公司 | Immunomodulatory combinations for cancer treatment |
| CN114617878A (en) * | 2022-05-16 | 2022-06-14 | 深圳大学 | Application of CK2 inhibitor in preparation of anti-aging drugs |
| RU2021114145A (en) * | 2018-10-19 | 2022-11-21 | Сенва Байосайенсиз, Инк. | COMBINATIONS FOR IMMUNOMODULATION IN THE TREATMENT OF CANCER |
| CN115480062A (en) * | 2021-06-15 | 2022-12-16 | 广州弘润生物科技有限公司 | Key drug target screening for de-differentiating CD8+ T cells into CD8+ TCM (TCM) and application of key drug target in drugs thereof |
-
2023
- 2023-05-10 CN CN202310520332.1A patent/CN116211860B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017070137A1 (en) * | 2015-10-20 | 2017-04-27 | Bristol-Myers Squibb Company | Combination of ck2 inhibitors and immune checkpoint modulators for cancer treatment |
| CN105560239A (en) * | 2015-12-30 | 2016-05-11 | 耿炜 | Use of CX4945 for preparation of drug having reversal effect on gastric cancer cisplatin-resistant radiation tolerance |
| TW201737940A (en) * | 2016-04-08 | 2017-11-01 | 基利科學股份有限公司 | Compositions and methods for treating cancer, inflammatory diseases and autoimmune diseases |
| CN112789292A (en) * | 2018-07-31 | 2021-05-11 | 皮里斯制药有限公司 | Novel fusion proteins specific for CD137 and PD-L1 |
| CN113015529A (en) * | 2018-10-19 | 2021-06-22 | 生华生物科技股份有限公司 | Immunomodulatory combinations for cancer treatment |
| RU2021114145A (en) * | 2018-10-19 | 2022-11-21 | Сенва Байосайенсиз, Инк. | COMBINATIONS FOR IMMUNOMODULATION IN THE TREATMENT OF CANCER |
| CN112274642A (en) * | 2020-10-15 | 2021-01-29 | 北京大学人民医院 | Application of CK2 inhibitor in preparation of medicine for treating rheumatoid arthritis |
| CN115480062A (en) * | 2021-06-15 | 2022-12-16 | 广州弘润生物科技有限公司 | Key drug target screening for de-differentiating CD8+ T cells into CD8+ TCM (TCM) and application of key drug target in drugs thereof |
| CN114617878A (en) * | 2022-05-16 | 2022-06-14 | 深圳大学 | Application of CK2 inhibitor in preparation of anti-aging drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116211860A (en) | 2023-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109294985B (en) | Culture medium system for NK cell in-vitro amplification and NK cell in-vitro amplification method | |
| CN107460167B (en) | Method for amplifying NK cells without trophoblasts | |
| EP1966369B1 (en) | Method for expansion of tumour-reactive t-lymphocytes for immunotherapy of patients with cancer | |
| CN103756963A (en) | Method used for in vitro proliferation of NK cells | |
| CN108697734B (en) | NK cells exhibiting adaptive phenotype and methods of making and using | |
| CN110520438A (en) | Oncolytic viral therapy | |
| JP2021523090A (en) | Methods and compositions for treating tumors | |
| Dong et al. | Autologous dendritic cells combined with cytokine-induced killer cells synergize low-dose chemotherapy in elderly patients with acute myeloid leukaemia | |
| Nakazawa et al. | Establishment of an efficient ex vivo expansion strategy for human natural killer cells stimulated by defined cytokine cocktail and antibodies against natural killer cell activating receptors | |
| JP2010220479A (en) | Method for culturing nk cell and use of the same | |
| CN116211860B (en) | Application of CK2 inhibitor CX4945 in preparation of medicines for preventing immune cell depletion in tumor treatment, inhibitor and combination | |
| WO2023165573A1 (en) | Culture medium formula for activating whole anti-tumor immune system and method for preparing agonist activated whole immune effector cells | |
| US20190160099A1 (en) | Pharmaceutical composition and use thereof | |
| CN104906575A (en) | Application of LSECtin as melanoma immunotherapy target | |
| CN112831468A (en) | TCM/TSCM cell for improving TIL cell induction and application | |
| WO1999018980A1 (en) | Cancer immunotherapy using allostimulated cells in a multiple sequential implantation strategy | |
| Gardam et al. | Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma | |
| CN113521270B (en) | EBV composite antigen, dendritic cell vaccine and application thereof | |
| EP2053123B1 (en) | Method of proliferating lak cell | |
| US20210008112A1 (en) | CIML NK cells and Methods Therefor | |
| CN116063556B (en) | IPS-derived CAR-NK cells and their use for the treatment of cancer | |
| CN116904400B (en) | Application of calicheamicin in optimization of in-vitro CAR/TCR-T cell product preparation process | |
| WO2023125696A2 (en) | Activated lymphocyte expansion method having stable and controllable quality, and anti-tumor use thereof | |
| EP4052716A1 (en) | Cancer therapy involving car-engineered t-cells and parvovirus h-1 | |
| CN109913413B (en) | PD-1 antibody loaded T cell in-vitro culture method, cell preparation and application thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: No. 47 Binshui Road, Huanhu West Road, Hexi District, Tianjin City, 300060 Patentee after: TIANJIN CANCER HOSPITAL(TIANJIN MEDICAL University CANCERINSTITUTE& Hospital) Patentee after: Cell Ecology Haihe Laboratory Address before: 2-1-101, Building 1-3, Bolong Industrial Park, north of Yuexin Road and east of Huixin Road, Binhai Science and Technology Park, Binhai High-tech Zone, Binhai New District, Tianjin 300450 Patentee before: Cell Ecology Haihe Laboratory Patentee before: TIANJIN CANCER HOSPITAL(TIANJIN MEDICAL University CANCERINSTITUTE& Hospital) |