CN115975922A - Bx795在制备nk-92细胞激活剂上的应用 - Google Patents
Bx795在制备nk-92细胞激活剂上的应用 Download PDFInfo
- Publication number
- CN115975922A CN115975922A CN202211613611.4A CN202211613611A CN115975922A CN 115975922 A CN115975922 A CN 115975922A CN 202211613611 A CN202211613611 A CN 202211613611A CN 115975922 A CN115975922 A CN 115975922A
- Authority
- CN
- China
- Prior art keywords
- cells
- cell
- cancer
- cell activator
- promotes
- 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.)
- Granted
Links
- 239000012190 activator Substances 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 5
- 101000665442 Homo sapiens Serine/threonine-protein kinase TBK1 Proteins 0.000 claims abstract description 11
- 102100038192 Serine/threonine-protein kinase TBK1 Human genes 0.000 claims abstract description 11
- 230000026731 phosphorylation Effects 0.000 claims abstract description 4
- 238000006366 phosphorylation reaction Methods 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims description 6
- 230000000259 anti-tumor effect Effects 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 83
- 210000000822 natural killer cell Anatomy 0.000 abstract description 14
- 206010028980 Neoplasm Diseases 0.000 abstract description 9
- 201000011510 cancer Diseases 0.000 abstract description 7
- 230000001093 anti-cancer Effects 0.000 abstract description 6
- 230000002147 killing effect Effects 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 210000002865 immune cell Anatomy 0.000 abstract description 2
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 8
- 230000006870 function Effects 0.000 description 5
- 235000020183 skimmed milk Nutrition 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 238000003119 immunoblot Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 102000055277 human IL2 Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000001939 mature NK cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明公开BX795在制备NK‑92细胞激活剂上的应用。NK(Nature killer)细胞是有效杀伤癌细胞和病毒感染细胞的天然免疫细胞。本发明公开了BX795对人源NK细胞株NK‑92的作用。经研究发现，BX795促进NK‑92细胞中TBK1/NAK(Ser172)的磷酸化，促进NK‑92与NK‑92之间和NK‑92与K562细胞之间的结合，并增强NK‑92细胞对K562细胞的杀伤作用。BX795提高NK‑92细胞的功能，这将为探索BX795在抗癌方面的作用提供了新的意义。
Description
技术领域
本发明属于探寻增强NK细胞功能的药物，涉及NK细胞治疗领域，涉及BX795在制备NK-92细胞激活剂上的应用，为治疗癌症提供新的思路。
背景技术
自然杀伤细胞(Natural killer，NK)是先天免疫系统的细胞毒性淋巴细胞，无需预先致敏就能非特异性杀伤肿瘤细胞或病毒感染细胞[1,2]。但是，在癌症患者中肿瘤细胞及其微环境通过多种逃逸机制来抑制NK细胞的抗肿瘤活性，造成NK细胞的功能受损[2]。随着对NK细胞的生物学和抗肿瘤功能认识的进展，NK细胞用于细胞治疗已被广泛研究和评论[1-3]。目前，NK细胞治疗的主要难题是难以获得足够数量的细胞和功能活跃并持久的NK细胞[1,2]。
NK-92细胞是来源于人恶性非霍奇金淋巴瘤患者的NK细胞，具有良好的NK细胞系特征，在实验室容易扩增[4-6]。NK-92细胞是被美国食品及药物管理局(FDA)批准用于临床试验的成熟NK细胞系，在临床试验中NK-92细胞得到广泛测试，确认是最具临床应用前景的细胞系[7-10]。而且，与从血液或其他来源分离的原代NK细胞相比，NK-92细胞系更容易获得和显著降低治疗成本[4,9,10]。然而，NK-92细胞的癌细胞特性引起了安全性问题，用于治疗之前需要放射处理细胞，这对体内的长期持久和整体治疗产生负面影响。[7,8]。
BX795是一种有效的选择性的TBK1抑制剂，有效地抑制各种癌细胞的功能[11,12]，如抑制口腔鳞状癌[13]、成神经细胞瘤[14]、膀胱癌[15]、肺癌[16]、黑色素瘤[17]和恶性胶质瘤[18]等。目前为止，已确定BX795抑制多种癌细胞的功能，但对NK细胞功能方面的研究还没有文献报道。
BX795能抑制癌细胞的功能。我们希望BX795能激活NK-92细胞的抗癌活性同时也能抑制癌症特性，以此避免放射带来的负面影响，有益于提高抗癌效率。
参考文献：
1.Guillerey C,Huntington ND,Smyth MJ(2016)Targeting natural killercells in cancer immunotherapy.NatImmunol 17:1025-1036.
2.Myers JA,Miller JS(2021)Exploring the NK cell platform for cancerimmunotherapy.Nat Rev Clin Oncol 18:85-100.
3.Luna JI,Grossenbacher SK,Murphy WJ,Canter RJ(2017)Targeting CancerStem Cells with Natural Killer Cell Immunotherapy.Expert Opin Biol Ther 17:313-324.
4.Klingemann H,Boissel L,Toneguzzo F(2016)Natural Killer Cells forImmunotherapy-Advantages of the NK-92 Cell Line over Blood NK Cells.FrontImmunol 7:91.
5.Tam YK,Martinson JA,Doligosa K,Klingemann HG(2003)Ex vivo expansionof the highly cytotoxic human natural killer-92 cell-line under current goodmanufacturing practice conditions for clinical adoptive cellularimmunotherapy.Cytotherapy 5:259-272.
6.Suck G,Odendahl M,Nowakowska P,Seidl C,Wels WS,et al.(2016)NK-92:an'off-the-shelf therapeutic'for adoptive natural killer cell-based cancerimmunotherapy.Cancer Immunol Immunother65:485-492.
7.Fabian KP,Hodge JW(2021)The emerging role of off-the-shelfengineered natural killer cells in targeted cancer immunotherapy.Mol TherOncolytics 23:266-276.
8.Zhang J,Zheng H,Diao Y(2019)Natural Killer Cells and CurrentApplications of Chimeric Antigen Receptor-Modified NK-92 Cells in TumorImmunotherapy.IntJ Mol Sci 20.
9.Shankar K,Capitini CM,Saha K(2020)Genome engineering of inducedpluripotent stem cells to manufacture natural killer cell therapies.Stem CellRes Ther 11:234.
10.Liu D,Tian S,Zhang K,Xiong W,Lubaki NM,et al.(2017)Chimericantigen receptor(CAR)-modified natural killer cell-based immunotherapy andimmunological synapse formation in cancer and HIV.Protein Cell 8:861-877.
11.AlamM,Ansari MM,Noor S,Mohammad T,Hasan GM,et al.(2022)Therapeutictargeting of TANK-binding kinase signaling towards anticancer drugdevelopment:Challenges and opportunities.IntJ Biol Macromol 207:1022-1037.
12.Alam M,Hasan GM,Hassan MI(2021)A review on the role of TANK-binding kinase 1 signaling in cancer.Int J Biol Macromol 183:2364-2375.
13.Bai LY,Chiu CF,Kapuriya NP,Shieh TM,Tsai YC,et al.(2015)BX795,aTBK1 inhibitor,exhibits antitumor activity in human oral squamous cellcarcinoma through apoptosis induction and mitotic phase arrest.Eur JPharmacol 769:287-296.
14.Chilamakuri R,Rouse DC,Yu Y,Kabir AS,Muth A,et al.(2022)BX-795inhibits neuroblastoma growth and enhances sensitivity towardschemotherapy.Transl Oncol 15:101272.
15.Chen W,Luo K,Ke Z,Kuai B,He S,et al.(2017)TBK1 Promote BladderCancer Cell Proliferation and Migration via Akt Signaling.J Cancer 8:1892-1899.
16.Cooper JM,Ou YH,McMillan EA,Vaden RM,Zaman A,et al.(2017)TBK1Provides Context-Selective Support of the Activated AKT/mTOR Pathway in LungCancer.Cancer Res 77:5077-5094.
17.Eskiocak B,McMillan EA,Mendiratta S,Kollipara RK,Zhang H,et al.(2017)Biomarker Accessible and Chemically Addressable Mechanistic Subtypes ofBRAF Melanoma.Cancer Discov 7:832-851.
18.Scuderi SA,Lanza M,Casili G,Esposito F,Colarossi C,et al.(2021)TBK1 Inhibitor Exerts AntiproliferativeEffect on GlioblastomaMultiformeCells.Oncol Res 28:779-790.
发明内容
本发明的目的是为了探索BX795在抗癌方面的更多意义，提供BX795对NK-92细胞的作用，弥补了BX795对抗癌细胞功能方面的研究空白。
第一方面，本发明提供BX795作为NK-92细胞激活剂在制备治疗肿瘤药物上的应用。
作为优选，BX795激活NK-92细胞中磷酸化TBK1/NAK。
作为优选，BX795促进NK-92细胞之间的结合。
作为优选，BX795促进NK-92之间的结合，以及NK-92与靶细胞之间的结合。
作为优选，靶细胞为K562细胞。BX795增强NK-92细胞对K562靶细胞的杀伤作用。
第二方面，本发明提供一种NK-92细胞激活剂，包括BX795。
作为优选，所述药物的剂型为医学上认可的任何一种剂型。
第三方面，本发明提供NK-92细胞激活剂在制备抗肿瘤药物中的应用。
第四方面，本发明提供一种抗肿瘤药物组合物，其特征在于所述药物组合物包括NK-92细胞激活剂或者其药学上可接受的盐或酯，以及药学上可接受的载体。
本发明用化合物BX795处理NK-92细胞，观察NK-92细胞的结合能力和对K562靶细胞的杀伤作用。经研究发现，BX795显著激活NK92细胞中磷酸化TBK1(Ser172)，促进NK-92与NK-92之间和NK-92与K562细胞之间的结合，并促进NK-92对K562靶细胞的杀伤作用。
本发明的有益效果：
BX795对癌细胞的直接抑制作用已有研究报道，但对抗癌免疫细胞方面的作用还不清楚。本发明确定了BX795可以激活NK-92细胞的功能，这将为拓宽BX795对抗癌方面的研究有一定的意义。
附图说明
图1、BX795处理NK-92细胞1小时和4小时后细胞中磷酸化TBK1(Ser172)蛋白表达的免疫印迹观察结果。
图2、BX795处理NK-92细胞4小时后细胞结合的显微镜观察结果。
图3、BX795促进NK-92与K562细胞的结合。用BX795处理1小时后显微镜观察NK-92与NK-92细胞之间和NK-92与K562靶细胞之间的结合。
图4、预先用CFDA-SE或Calcein-AM荧光探针标记的K562细胞与NK-92细胞(没有进行标记)共培养，并处理1小时的BX795后流式细胞仪观察荧光强度(A)，折线图分析荧光强度的变化(B和C)。**为差异极显著。
图5、用Calcein-AM荧光探针标记NK-92和K562细胞后处理4小时的BX795(10μM)观察荧光强度变化(A和B)；用Calcein-AM荧光探针分别标记NK-92和K562细胞后共培养并处理4小时的BX795，收集细胞用流式细胞仪观察荧光强度(C和D)。*为差异显著，**为差异极显著。
具体实施方式
下面结合附图对本发明做进一步的分析。
实施例1、细胞培养：
NK-92(CRL-2407)和K562(CCL-243)细胞从American Type Culture Collection(ATCC,USA)公司购买。NK-92细胞培养用α-MEM培养基(MA0216,Meilunbio)+20％的胎牛血清(SH30406.05,HyClone)+10nM重组的人白介素2(200-02,PeproTech)。K562细胞的培养由RPMI1640培养液(MA0215,Meilunbio)中加10％的胎牛血清(SH30406.05,HyClone)。所有培养液中都加青霉素-链霉素(SV30010,HyClone)，细胞培养条件为37℃、5％的CO2和充足的湿度。
实施例2、免疫印迹实验：
NK-92细胞分MEDIA组(正常培养组)、DMSO组(空白对照组)和不同浓度(2.5、5.0和10.0μM)的BX795(S1274，Selleck)组，处理1小时和4小时后收集细胞，1500rpm离心5分钟。彻底吸除上清液后，用高效RIPA组织/细胞裂解液(R0010，Solarbio)+1mM的PMSF(现用现加)裂解细胞，在冰上孵育30分钟后，4℃、12000rpm速度离心30分钟。每组样品中吸取同等体积的上清液，加1×上样缓冲液混合，在100℃反应5分钟后急速放冰上冷却。
配制10％的SDS-PAGE胶，用BioRad电泳仪在80V电泳分离蛋白，在100V电压转印蛋白75分钟到PVDF膜(IPVH00010，Millipore)。PVDF膜用5％的脱脂乳(232100，BD Difco)(用1×PBS配制脱脂乳)封闭1小时后，更换成Phospho-TBK1(Ser172)(#5483，CST)抗体(用5％的脱脂乳稀释抗体1：1000)在4℃冰箱的摇床孵育过夜。次日先用TBS-T(C520009-0500，生工)在摇床清洗5分钟×3次，继续在室温摇床孵育Anti-rabbit IgG HRP(#7074，CST)抗体(5％脱脂乳稀释抗体1：3000)3～4小时，再用TBS-T清洗5分钟×3次。在暗室用化学发光HRP底物(ECL发光液)(WBKLS0500，Millipore)反应后，在医用X射线胶片(6535876，Carestream)上显影和定影。β-Actin(#3700，CST)是内参抗体，二抗是用Anti-mouse IgGHRP-linkedAntibody(#7076，CST)。
BX795激活NK-92细胞中TBK1(Ser172)的磷酸化结果见图1。用BX795处理NK-92细胞1小时和4小时后免疫印迹观察细胞中磷酸化TBK1(Ser172)蛋白的表达。
实施例3、细胞结合实验：
K562细胞分Media组、DMSO组和不同浓度(2.5、5.0和10.0μM)的BX795组。处理1小时后每组细胞再分两组，分别用CFDA-SE细胞增殖与示踪检测试剂(C0051，Beyotime)和钙黄绿素-AM(Calcein-AM)(C2012，Beyotime)按照产品使用说明书标记细胞，用BeckmanCytoFlex流式细胞分析仪分析细胞的荧光强度。
预先用CFDA-SE或Calcein-AM荧光标记的K562细胞与NK-92细胞混在一起(NK-92:K562比例为2:1)，分Media组、DMSO组和不同浓度(2.5、5.0和10.0μM)的BX795组。共培养1小时后，小心地收集细胞(避免强烈吹打或震荡)，用Beckman CytoFlex流式细胞分析仪分析细胞的荧光强度。
从图2可知，BX795促进NK-92细胞间的结合。
从图3可知，BX795促进NK-92与K562细胞的结合。
从图4可知，流式细胞仪验证BX795促进NK-92与K562细胞的结合。
实施例4、NK-92对K562细胞的毒性实验：
收集NK-92和K562细胞计数，按产品使用说明书对细胞进行Calcein-AM标记。标记的细胞清洗两次后，用BX795(10μM)处理4小时，观察有没有影响NK-92和K562细胞的荧光强度。
预先用Calcein-AM荧光标记的NK-92和K562细胞混在一起(NK-92:K562比例设计5:1和10:1两个条件)，并处理不同浓度(2.5、5.0和10.0μM)的BX795共培养4小时后收集细胞，用Beckman CytoFlex流式细胞分析仪分析荧光强度。
从图5可知，BX795促进NK-92对K562细胞的毒性作用。
Claims (9)
1.BX795在制备NK-92细胞激活剂上的应用。
2.如权利要求1所述的应用，其特征在于BX795激活NK-92细胞中磷酸化TBK1/NAK。
3.如权利要求1或2所述的应用，其特征在于BX795促进NK-92细胞之间的结合。
4.如权利要求1或2所述的应用，其特征在于BX795促进NK-92之间的结合，以及NK-92与靶细胞之间的结合。
5.如权利要求1或2所述的应用，其特征在于靶细胞为K562细胞。
6.一种NK-92细胞激活剂，其特征在于包括BX795。
7.如权利要求6所述的一种NK-92细胞激活剂，其特征在于所述药物的剂型为医学上认可的任何一种剂型。
8.如权利要求6所述的一种NK-92细胞激活剂在制备抗肿瘤药物中的应用。
9.一种抗肿瘤药物组合物，其特征在于所述药物组合物包括NK-92细胞激活剂或者其药学上可接受的盐或酯，以及药学上可接受的载体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211613611.4A CN115975922B (zh) | 2022-12-15 | 2022-12-15 | Bx795在制备nk-92细胞激活剂上的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211613611.4A CN115975922B (zh) | 2022-12-15 | 2022-12-15 | Bx795在制备nk-92细胞激活剂上的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115975922A true CN115975922A (zh) | 2023-04-18 |
| CN115975922B CN115975922B (zh) | 2024-06-28 |
Family
ID=85964012
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211613611.4A Active CN115975922B (zh) | 2022-12-15 | 2022-12-15 | Bx795在制备nk-92细胞激活剂上的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115975922B (zh) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018022646A1 (en) * | 2016-07-25 | 2018-02-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of producing modified natural killer cells and methods of use |
| CN108291221A (zh) * | 2015-09-30 | 2018-07-17 | 维萨列克斯股份有限公司 | 向天然杀伤细胞、造血干细胞和巨噬细胞的增强化基因递送 |
| CN108888623A (zh) * | 2018-08-14 | 2018-11-27 | 青岛大学 | 酪氨酸蛋白激酶jak2抑制剂bx795的应用 |
| US20200392457A1 (en) * | 2016-07-25 | 2020-12-17 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Methods of producing modified natural killer cells and methods of use |
| WO2022251584A1 (en) * | 2021-05-28 | 2022-12-01 | St. Jude Children's Research Hospital, Inc. | Methods and compositions for transduction of nk cells |
| CN115466726A (zh) * | 2022-09-05 | 2022-12-13 | 北京景达生物科技有限公司 | 一种nk细胞的高效基因转导方案 |
| CN115778958A (zh) * | 2022-11-11 | 2023-03-14 | 杭州师范大学 | Bx795在制备治疗慢性髓性白血病药物上的应用 |
| CN115919865A (zh) * | 2022-12-15 | 2023-04-07 | 杭州师范大学 | Bx795在制备抑癌蛋白pten激活剂上的应用 |
-
2022
- 2022-12-15 CN CN202211613611.4A patent/CN115975922B/zh active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108291221A (zh) * | 2015-09-30 | 2018-07-17 | 维萨列克斯股份有限公司 | 向天然杀伤细胞、造血干细胞和巨噬细胞的增强化基因递送 |
| WO2018022646A1 (en) * | 2016-07-25 | 2018-02-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of producing modified natural killer cells and methods of use |
| US20200392457A1 (en) * | 2016-07-25 | 2020-12-17 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Methods of producing modified natural killer cells and methods of use |
| CN108888623A (zh) * | 2018-08-14 | 2018-11-27 | 青岛大学 | 酪氨酸蛋白激酶jak2抑制剂bx795的应用 |
| WO2022251584A1 (en) * | 2021-05-28 | 2022-12-01 | St. Jude Children's Research Hospital, Inc. | Methods and compositions for transduction of nk cells |
| CN115466726A (zh) * | 2022-09-05 | 2022-12-13 | 北京景达生物科技有限公司 | 一种nk细胞的高效基因转导方案 |
| CN115778958A (zh) * | 2022-11-11 | 2023-03-14 | 杭州师范大学 | Bx795在制备治疗慢性髓性白血病药物上的应用 |
| CN115919865A (zh) * | 2022-12-15 | 2023-04-07 | 杭州师范大学 | Bx795在制备抑癌蛋白pten激活剂上的应用 |
Non-Patent Citations (2)
| Title |
|---|
| 廖春香: "TLR3激动剂对体外NK细胞抗肿瘤活性的影响及机制", 贵州医科大学学报, vol. 46, no. 1, 18 January 2021 (2021-01-18), pages 9 - 15 * |
| 张军;董雅璐;: "靶向MSLN的CAR-NK-92细胞在胃癌中的抗肿瘤活性研究", 中国医药导报, no. 19, 5 July 2020 (2020-07-05), pages 17 - 21 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115975922B (zh) | 2024-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2862433T3 (es) | Uso de linfocitos infiltrantes de médula ósea alogénicos tratados con ciclofosfamida postrasplante para aumentar la inmunidad antitumoral | |
| Khammari et al. | Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients | |
| JP7235259B2 (ja) | Ｇｖｈｄ又は腫瘍を治療するための骨髄系由来サプレッサー細胞のインフラマソーム活性化の調節 | |
| US20240325538A1 (en) | Tumor infiltration lymphocyte culture medium and application thereof | |
| Strizova et al. | The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma | |
| MIZUTANI et al. | Sensitization of human bladder cancer cells to Fas-mediated cytotoxicity by cis-diamminedichloroplatinum (II) | |
| Hu et al. | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling | |
| CN115975922A (zh) | Bx795在制备nk-92细胞激活剂上的应用 | |
| Xu et al. | Synergistic effects of low‑dose chemotherapy and T cells in renal cell carcinoma | |
| Nath et al. | Immunotherapeutic potential of ethanolic olive leaves extract (EOLE) and IL-28B combination therapy in ENU induced animal model of leukemia | |
| Franzolin et al. | PlexinB1 inactivation reprograms immune cells in the tumor microenvironment, inhibiting breast cancer growth and metastatic dissemination | |
| Huang et al. | Polyinosinic-cytidylic acid as an adjuvant on natural killer-and dendritic cell-mediated antitumor activities | |
| CN112516298B (zh) | 一种靶向EpCAM-CART细胞与hsBCL9CT-24的组合在抗肿瘤中的应用 | |
| KR102300846B1 (ko) | 면역 활성 개선용 조성물 및 이의 방법 | |
| Keenan | Identifying the therapeutic potential of novel compounds in the treatment of Glioblastoma Multiforme. | |
| Zeng | Expression of PD-L1, CTLA-4, and LAG-3 in human thyroid carcinoma | |
| URZÌ et al. | LEMON-DERIVED EXTRACELLULAR VESICLES EXERT ANTI-INFLAMMATORY EFFECTS BY INHIBITING THE ERK/NF-KB PATHWAY. | |
| CN118236361A (zh) | 牛磺酸联合化疗药物在制备抗肿瘤药物中的应用 | |
| Sugiyama et al. | Effects of serum immunosuppressive factors on antitumor cytotoxicity of interleukin 2‐induced lymphocytes | |
| WO2015179287A2 (en) | Z cells activated by zinc finger-like protein and uses thereof in cancer treatment | |
| KR20240131924A (ko) | 항-EGFR 항체의약품과 병용하는 자연살해세포의 TKIs 내성 비소세포폐암 치료방법 | |
| CN117801061A (zh) | 一种多肽及其在til中的应用 | |
| CA3227128A1 (en) | Universal receptor immune cell therapy | |
| KR20230084177A (ko) | 결핵균 추출물의 신규 용도 | |
| WO2022229264A2 (en) | Methods and uses |
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 |