CN108085340B - 一种同时表达靶向cd19和cd20的car与pd1-cd28嵌合受体的慢病毒载体 - Google Patents
一种同时表达靶向cd19和cd20的car与pd1-cd28嵌合受体的慢病毒载体 Download PDFInfo
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Abstract
本发明涉及分子生物学领域,具公开了一种同时表达靶向CD19和CD20的CAR与PD1‑CD28嵌合受体的慢病毒载体。所述慢病毒载体通过同时高效表达靶向CD19和CD20的CAR和PD1‑CD28嵌合体,使该载体感染的T细胞不仅可以靶向识别表达CD19和CD20的肿瘤细胞,而且可以解除PD‑L1/PD1介导的免疫抑制,从而发挥更强地杀伤肿瘤细胞的能力。进一步地,本发明优化了载体中关键元件的选择和连接顺序,提高靶向CD19和CD20的CAR和PD1‑CD28嵌合体在人类T细胞中的表达效率。
Description
技术领域
本发明涉及分子生物学领域,具体地说,涉及一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体。
背景技术
近年来,抗CD19的CAR-T在治疗复发,耐药,难治B细胞白血病和淋巴瘤方面取得了举世瞩目的成就,引起世界各国肿瘤临床医生的极大兴趣。但是仅靶向CD19的CAR-T治疗B细胞来源肿瘤会导致肿瘤细胞CD19低表达或不表达,从而导致肿瘤细胞免疫逃逸而产生复发和耐药。因此同时靶向CD19和CD20的CAR可以同时靶向B细胞来源肿瘤的CD19和CD20两个靶点,因此对于B细胞来源肿瘤尤其是CD19CAR-T治疗失败的患者,双靶点CAR-T会取得较好的治疗效果。CD19和CD20是B细胞系的细胞,包括正常的B细胞,前B细胞,B细胞淋巴瘤和白血病细胞,特异性表达的两个膜蛋白,其他细胞和组织都不表达CD19和CD20。研究表明,阻断PD-L1/PD1介导的免疫抑制将会是CAR-T成功用于治疗恶性肿瘤的关键。
阻断PD-L1和PD1的结合,理论上就可以消除PD1信号对T细胞的抑制,激活T细胞的免疫反应,起到抗肿瘤的效果。目前,FDA批准了两个抗PD1的单抗Nivolumab和Pembrolizumab用于治疗其他疗法已失败的转移性非小细胞肺癌和黑色素瘤。虽然我国黑色素瘤的发病率并不高,但肺癌是我国第一大癌,同时也是死亡率最高的癌症。其中的非小细胞肺癌,生存率极低。5年生存率不容乐观。目前,国家食品药品监督总局(CFDA)尚未批准Nivolumab和Pembrolizumab在国内临床使用。而且Nivolumab和Pembrolizumab需要多次使用,对大多数患者来说,医疗负担过重。
针对PD-L1的单抗也能起到类似的抗肿瘤效果。根据目前已经报道的临床研究,MPDL3280A(anti-PD-L1人源单抗)在治疗黑色素瘤,非小细胞肺癌,直结肠癌(colorectalcancer)和膀胱癌(bladder cancer)都取得了不同程度的疗效。MEDI4736是另外一个人源抗PD-L1单克隆抗体,它能阻断PD-L1和PD1的结合,使得T细胞能够识别和杀死肿瘤细胞。对于MEDI4736的临床抗肿瘤效果正在多个中心展开,其中也包括非小细胞性肺癌和头颈部肿瘤。
鉴于抗PD-L1/PD1抗体免疫治疗在我国的应用问题,急需提供一种可替代的治疗产品及方法。
发明内容
为了解决现有技术中存在的问题,本发明的目的是提供一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体及其构建方法与应用。
为了实现本发明目的,本发明的技术方案如下:
第一方面,本发明提供一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体。
PD1和CD28都属于CD28蛋白家族的成员。T细胞激活不仅需要抗原结合到TCR(T细胞受体)激活的信号,同时还需要共刺激分子(如CD28)提供的防止免疫无能(anergy)的信号。CD28是CD4+TH和CD8+CTL细胞的主要共刺激受体,而PD1是防止活化的T细胞免疫过激和自身免疫病的关键免疫闸门分子。研究发现,融合CD28膜外区和PD1膜内区的嵌合蛋白表现出类似于天然PD1分子抑制T细胞免疫反应的活性。相对应的,把PD1的膜外区和CD28的跨膜区和膜内区融合在一起,形成的嵌合蛋白能够结合PD-L1,但却促进T细胞激活,包括细胞因子释放增加,细胞增殖增加,细胞杀伤力增强。回输表达PD1-CD28嵌合受体的T细胞给负荷肿瘤的小鼠,能够彻底清除肿瘤。这些试验说明这两个蛋白的不同功能区可以很好的兼容在一起,组合形成一个新的,能够调节T细胞免疫反应的人工受体。
进一步研究发现,PD1-CD28嵌合受体能够把PD-L1/PD1传导的本来是抑制T细胞活性的信号,转换成刺激T细胞激活的信号。而且,肿瘤组织表达大量PD-L1,PD1-CD28嵌合受体借助于PD-L1提供的信号,化抑制为刺激,促进T细胞的抗肿瘤活性。
本发明将靶向CD19和CD20的CAR与PD1-CD28嵌合受体共同构建于同一慢病毒载体进而转入患者T细胞,使该基因修饰的T细胞不仅可以靶向识别表达CD19和CD20的肿瘤细胞,还可以解除肿瘤细胞表达的PD-L1对T细胞的免疫抑制,实现了良好的抗肿瘤效果。
进一步地,由于慢病毒感染外周血T细胞的效率普遍不高,而且多个目的基因在同一载体上表达时,所表达的蛋白活性及表达效率亦会下降。
为了促进靶向CD19和CD20的CAR和PD1-CD28嵌合受体在T细胞中均可进行高效的表达,本发明进一步优选了慢病毒载体启动子种类以及这两个目的基因的连接方式,以求对T细胞发挥最佳的感染效率。
基于此目的,本发明通过在慢病毒表达载体中,使两个目的基因共用一个启动子EF1α,并在两者间使用Furin-linker-spacer-F2A进行连接,使得该慢病毒载体产生的慢病毒可以高效感染外周血T细胞,而且靶向CD19和CD20的CAR与PD1-CD28嵌合体可以分别表达于该T细胞表面。
更为具体地说:所述慢病毒载体携带两个目的基因,先通过转染试剂转染293ft细胞产生慢病毒,然后慢病毒感染外周血T细胞,进而将两个目的基因整合进T细胞基因组,从而实现这两个目的基因在T细胞内表达。
所述Furin-linker-spacer-F2A在本文中可简称为2A肽,在图3中表示为F2A。
由于Furin和F2A肽的剪切作用,上游蛋白(靶向CD19和CD20的CAR)的C端仅含有1到3个额外的氨基酸残基,下游蛋白(PD1-CD28嵌合体)的N端仅含有额外的脯氨酸残基。经实验研究后,这些氨基酸残基不影响这两个蛋白正常表达。
进一步地,所述慢病毒载体优选为所述慢病毒载体选自启动子为EF1α的慢病毒载体。如此,则无需对慢病毒载体的启动子进行替换,直接使用慢病毒载体自带的EF1α启动子即可。
自带EF1α启动子的慢病毒载体可通过商业途径购买获得。例如,在本发明的具体实施方式中,所使用的自带EF1α启动子的慢病毒载体为pCDH-EF1-Luc2-T2A-tdTomato,购自武汉淼灵生物科技有限公司。
所述靶向CD19和CD20的CAR的氨基酸序列如SEQ ID NO.1所示,其编码基因的核苷酸序列如SEQ ID NO.2所示;所述2A肽的氨基酸序列如SEQ ID NO.3所示,其编码基因的核苷酸序列如SEQ ID NO.4所示;所述PD1-CD28的氨基酸序列如SEQ ID NO.5所示,其编码基因的核苷酸序列如SEQ ID NO.7所示。
第二方面,本发明提供前述慢病毒载体的构建方法,包括如下步骤:
(1)将表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的核苷酸序列使用Furin-linker-spacer-F2A进行连接,合成融合基因,合成所述融合基因时在其两端分别包含XbaI和SalI酶切位点,并将其装载在质粒上;
(2)利用XbaI和SalI双酶切步骤(1)所述质粒,切胶回收目的基因片段;
(3)利用XbaI和SalI双酶切慢病毒原始载体,切胶回收的载体片段;
(4)利用DNA连接酶将步骤(2)回收的目的基因片段与步骤(3)回收的载体片段连接,即得。
进一步地,为了进一步提高两个目的基因的表达效率,本实验室又对比了多个在T细胞中高效表达的启动子。而后研究发现,EF1ɑ启动子相较于其他本领域常用的强启动子,具有显著优势。
因此在本发明所述方法中,优选所述慢病毒原始载体自带EF1α启动子。
第三方面,本发明提供了前述慢病毒载体在抗肿瘤治疗中的应用,以及其在制备抗肿瘤药物中的应用。
本发明涉及到的原料或试剂均为普通市售产品,涉及到的操作如无特殊说明均为本领域常规操作。
在符合本领域常识的基础上,上述各优选条件,可以相互组合,得到具体实施方式。
本发明的有益效果在于:
本发明提供了一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体,使该载体感染的T细胞不仅可以靶向识别表达CD19和CD20的肿瘤细胞,而且可以解除PD-L1/PD1介导的免疫抑制,从而发挥更强地杀伤肿瘤细胞的能力。进一步地,本发明优化了载体中关键元件的选择和连接顺序,使得这两个目的基因均能在人类T细胞中高效表达。
附图说明
图1为本发明实施例2中CD19&CD20 CAR和PD1-CD28在载体中的多种连接方式的组合示意图。
图2为实施例2中18种慢病毒载体感染外周血T细胞后表达CD19&CD20 CAR和PD1-CD28 T细胞的百分比,其中,纵坐标表示表达这两个目的基因的T细胞百分比。
图3为实施例2中优选的慢病毒载体结构示意图,其中,F2A表示Furin-linker-spacer-F2A的组合。
图4为实施例3中两个目的基因位置调换前后的慢病毒载体感染外周血T细胞后表达CD19&CD20 CAR和PD1-CD28 T细胞的百分比,17-1表示图2中的17号载体,17-2表示图2中的17号载体两个目的基因调换位置后的载体,其中,纵坐标表示表达这两个目的基因的T细胞百分比。
具体实施方式
下面将结合实施例对本发明的优选实施方式进行详细说明。需要理解的是以下实施例的给出仅是为了起到说明的目的,并不是用于对本发明的范围进行限制。本领域的技术人员在不背离本发明的宗旨和精神的情况下,可以对本发明进行各种修改和替换。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
本实施例用于说明本发明所述慢病毒载体的构建方法。
1、原料
原始载体pCDH-EF1-Luc2-T2A-tdTomato:购自武汉淼灵生物科技有限公司。
XbaI和SalI内切酶:购自New England Biolabs(Beijing)LTD.。
2、载体的构建
(1)将表达靶向CD19&CD20的CAR与PD1-CD28嵌合受体的核苷酸序列使用Furin-linker-spacer-F2A进行连接,合成融合基因,合成这段基因时在两端分别包含XbaI和SalI酶切位点,并装载在pUC57载体上;
(2)XbaI和SalI双酶切包含目的基因的pUC57载体,切胶回收目的基因片段;
(3)利用XbaI和SalI双酶切原始载体pCDH-EF1-Luc2-T2A-tdTomato,切胶回收约6.5kb的载体片段;
(4)用DNA连接酶连接回收的目的基因片段和载体片段,即得。
实施例2
本实施例用于说明在构建载体的过程中,对载体中关键元件的选择和连接顺序的优化。
本实施例对多种在T细胞高效表达的启动子以及两个目的基因的主要的连接方式进行组合尝试(详见图1)。
合成图1中的18种目的基因序列,通过XbaI和SalI双酶切构建于pCDH-EF1-Luc2-T2A-tdTomato载体,将18种构建好的慢病毒载体进行慢病毒包装,进而感染外周血T细胞,靶向CD19&CD20的CAR和PD-1的抗体进行流式染色,通过流式细胞仪进行分析。结果如表1和图2所示。
需要说明的是,由于pCDH-EF1-Luc2-T2A-tdTomato载体自带启动子EF1α,当使用其他启动子时,需首先在其他启动子序列的两端引入包含ClaI和XbaI的酶切位点序列,然后通过ClaI和XbaI双酶切合成的核苷酸序列,同时使用这两个酶双酶切pCDH-EF1-Luc2-T2A-tdTomato载体获得约9kb的载体片段,然后将双酶切后的启动子序列和酶切后的载体片段通过DNA连接酶进行连接,从而构建包含不同启动子的慢病毒载体。
表1 18种慢病毒载体感染外周血T细胞后CD19&CD20 CAR和PD1-CD28阳性T细胞比例
通过比较实验结果,发现17号载体的构建方式能够实现CD19&CD20 CAR和PD1-CD28在T细胞中均进行高效表达,且意外发现其表达比例显著高于其他组合方式。
因此,本发明优选该组合方式构建所述慢病毒载体(图3)。
实施例3
本实施例与实施例1的区别在于,将CD19&CD20 CAR和PD1-CD28在载体中的基因位置进行调换,实验发现,位置调换后,目的蛋白的表达效率不受影响(图4)。
应当理解的是,对上述实施例所用试剂或原料的用量进行等比例扩大或者缩小后的技术方案,与上述实施例的实质相同。
虽然,上文中已经用一般性说明及具体实施方案对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
序列表
<110> 北京市肿瘤防治研究所
<120> 一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体
<141> 2017-11-30
<160> 6
<170> SIPOSequenceListing 1.0
<210> 1
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<212> PRT
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180 185 190
Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln
195 200 205
Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr
210 215 220
Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr
225 230 235 240
Tyr Cys Ala Arg Ser Asn Tyr Tyr Gly Ser Ser Tyr Trp Phe Phe Asp
245 250 255
Val Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly
260 265 270
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
275 280 285
Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln
290 295 300
Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr
305 310 315 320
Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu
325 330 335
Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys
340 345 350
Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu
355 360 365
Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala
370 375 380
Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln
385 390 395 400
Gly Thr Ser Val Thr Val Ser Ser Gly Ser Thr Ser Gly Ser Gly Lys
405 410 415
Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Asp Ile Gln Met Thr Gln
420 425 430
Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser
435 440 445
Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln
450 455 460
Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu
465 470 475 480
His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
485 490 495
Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr
500 505 510
Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr
515 520 525
Lys Leu Glu Ile Thr Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys
530 535 540
Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
545 550 555 560
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
565 570 575
Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp
580 585 590
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
595 600 605
Glu Gln Phe Gln Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
610 615 620
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
625 630 635 640
Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
645 650 655
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu
660 665 670
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
675 680 685
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
690 695 700
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
705 710 715 720
Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn
725 730 735
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
740 745 750
Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Met Phe Trp Val Leu Val
755 760 765
Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala
770 775 780
Phe Ile Ile Phe Trp Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile
785 790 795 800
Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp
805 810 815
Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu
820 825 830
Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly
835 840 845
Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr
850 855 860
Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys
865 870 875 880
Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys
885 890 895
Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg
900 905 910
Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala
915 920 925
Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg
930 935 940
<210> 2
<211> 2832
<212> DNA
<213> Artificial Sequence
<400> 2
atgctgctgc tcgtcaccag cctgctcctc tgtgaactgc ctcatcccgc tttcctcctg 60
atccccgata tcgtgctcac ccagagcccc gccattctca gcgcttcccc cggagaaaag 120
gtgacaatga cctgtagagc ttcctccagc gtgaactaca tggattggta ccagaagaag 180
cctggcagct cccccaaacc ctggatttac gccacaagca acctggcctc cggcgtgcct 240
gccagattca gcggatccgg cagcggcaca tcctatagcc tgaccatctc cagggtggag 300
gccgaggacg ctgctaccta ctactgtcaa cagtggtcct tcaatccccc tacctttggc 360
ggcggcacaa aattagaaat caaaggctcc accagcggcg gtggatctgg cgggggctct 420
ggaggtggcg ggtccagcga agtgcaactg cagcaaagcg gagccgagct ggtgaaaccc 480
ggagctagcg tgaagatgtc ctgcaaggct agcggctaca catttacatc ctacaacatg 540
cattgggtga aacagacccc tggccagggc ttagaatgga ttggcgctat ttaccctggc 600
aacggagaca catcctacaa tcagaagttc aagggaaagg ccaccctcac agccgataag 660
tccagcagca cagcctatat gcagctgtcc agcctgacca gcgaggacag cgccgactac 720
tactgcgcca ggtccaacta ctatggaagc agctactggt ttttcgacgt gtggggcgcc 780
ggaaccacag tgacagtctc cagcggcggc ggaggaagcg gaggaggcgg atccggaggc 840
ggaggctccg gcggcggagg cagcgaagtg aagctccagg agagcggccc cggactcgtg 900
gcccctagcc agtccctgtc cgtcacctgc accgtctccg gcgtgtccct gcctgattac 960
ggcgtgagct ggatcaggca acctcctaga aaaggcctgg agtggctggg agtgatttgg 1020
ggctccgaaa ccacctacta taactccgcc ctgaagtcca ggctgaccat tatcaaggac 1080
aatagcaagt cccaggtgtt tctcaagatg aacagcctcc agaccgacga tacagccatt 1140
tattactgcg ctaaacacta ctactacggc ggctcctatg ctatggacta ctggggccag 1200
ggaacatccg tgaccgtcag cagcggaagc acatccggca gcggcaaacc cggcagcgga 1260
gagggaagca caaagggaga catccagatg acccagacaa ccagcagcct gtccgcctcc 1320
ctgggagaca gagtgacaat cagctgcagg gcctcccaag atatcagcaa gtatctcaac 1380
tggtatcagc agaaacccga cggcacagtc aaactgctga tttatcacac aagcaggctc 1440
cacagcggcg tccccagcag gttctccgga tccggcagcg gcaccgacta cagcctgacc 1500
atcagcaacc tggaacagga ggacatcgct acctatttct gccagcaggg caacaccctc 1560
ccttatacat tcggaggagg caccaagtta gaaatcaccg aatccaagta cggccccccc 1620
tgccctcctt gtcctgctcc cgaattcgaa ggcggcccta gcgtcttcct gttccccccc 1680
aagcccaagg ataccctgat gatcagcaga acccctgaag tcacctgcgt ggtcgtggat 1740
gtctcccagg aggatcctga ggtgcagttc aactggtacg tcgatggcgt ggaagtgcac 1800
aacgccaaaa ccaaacctag ggaggaacaa ttccagtcca catacagagt cgtcagcgtg 1860
ctgacagtcc tgcatcagga ttggctgaac ggcaaggagt acaagtgtaa agtgagcaac 1920
aagggcctgc ctagcagcat tgagaagaca atttccaagg ccaaaggaca gcccagggaa 1980
cctcaagtgt acacactccc tcccagccag gaagaaatga ccaagaacca ggtgtccctg 2040
acatgcctgg tcaagggatt ctatccctcc gacatcgccg tcgaatggga gtccaacggc 2100
cagcccgaaa acaactacaa gaccacccct cccgtgctgg acagcgatgg cagcttcttt 2160
ctctacagca gactgaccgt cgataagagc agatggcaag agggcaatgt gttctcctgt 2220
agcgtgatgc acgaagctct gcacaaccac tatacacaga agtccctgag cctgagcctg 2280
ggaaaaatgt tctgggtcct cgtcgtggtg ggaggcgtgc tcgcttgcta ctccctgctc 2340
gtgaccgtcg ccttcatcat cttctgggtg aagagaggca ggaaaaagct gctctatatc 2400
ttcaagcagc ccttcatgag gcccgtgcag acaacacaag aggaggacgg ctgcagctgc 2460
agatttcctg aggaggagga gggaggctgc gagctcagag tcaagtttag caggagcgct 2520
gacgcccctg cctatcagca gggccagaac cagctctaca atgagctgaa cctgggaagg 2580
agggaagagt acgacgtgct cgacaaaaga aggggaaggg accccgagat gggcggaaaa 2640
cccagaagga agaatcctca ggagggcctg tataatgagc tgcagaagga caagatggcc 2700
gaggcctaca gcgagattgg catgaaagga gagaggagaa ggggcaaagg ccatgacgga 2760
ctgtaccaag gcctgtccac cgccaccaag gatacctatg atgccctgca catgcaggct 2820
ctgcctccca gg 2832
<210> 3
<211> 44
<212> PRT
<213> Artificial Sequence
<400> 3
Arg Ala Lys Arg Gly Lys Pro Ile Pro Asn Pro Leu Leu Gly Leu Asp
1 5 10 15
Ser Thr Ser Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu
20 25 30
Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro
35 40
<210> 4
<211> 132
<212> DNA
<213> Artificial Sequence
<400> 4
agggccaaga ggggcaagcc catccccaac cccctgctgg gcctggacag caccagcggc 60
agcggcgtga agcagaccct gaacttcgac ctgctgaagc tggccggcga cgtggagagc 120
aaccccggcc cc 132
<210> 5
<211> 235
<212> PRT
<213> Artificial Sequence
<400> 5
Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln
1 5 10 15
Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp
20 25 30
Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp
35 40 45
Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val
50 55 60
Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala
65 70 75 80
Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg
85 90 95
Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg
100 105 110
Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu
115 120 125
Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val
130 135 140
Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Cys Pro Ser Pro Leu
145 150 155 160
Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly
165 170 175
Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe
180 185 190
Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn
195 200 205
Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr
210 215 220
Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser
225 230 235
<210> 7
<211> 708
<212> DNA
<213> Artificial Sequence
<400> 7
atgcagattc cccaggcccc ttggcctgtg gtgtgggccg tgctgcagct gggatggagg 60
cctggctggt tcctggacag ccccgacaga ccctggaatc cccccacctt ttcccctgcc 120
ctgctcgtgg tgacagaggg cgacaacgcc accttcacct gcagcttctc caacaccagc 180
gagagcttcg tcctgaactg gtacaggatg agccccagca accagaccga caagctggcc 240
gccttccctg aggacagaag ccagcccggc caggactgca ggtttagagt gacccagctg 300
cccaatggca gagacttcca catgagcgtg gtgagggcca gaaggaatga cagcggcacc 360
tatctgtgcg gcgccatcag cctggctcct aaagcccaga tcaaggagtc cctgagggcc 420
gagctgaggg tgaccgagag gagagctgaa gtgcccaccg ctcactgccc ctcccctctg 480
tttcccggcc ctagcaaacc cttctgggtg ctggtggtgg tgggcggagt gctggcctgc 540
tacagcctcc tggtgaccgt cgccttcatc atcttctggg tgagaagcaa gaggagcaga 600
ctcctgcaca gcgactacat gaacatgacc cctaggaggc ctggccccac cagaaagcat 660
taccagcctt acgccccccc cagagacttt gccgcctaca ggtcctga 708
Claims (8)
1.一种同时表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的慢病毒载体,其特征在于,所述靶向CD19和CD20的CAR的氨基酸序列如SEQ ID NO.1所示,所述PD1-CD28嵌合受体的氨基酸序列如SEQ ID NO.5所示。
2.根据权利要求1所述的慢病毒载体,其特征在于,将表达靶向CD19和CD20的CAR与PD1-CD28嵌合受体的核苷酸序列使用Furin-linker-spacer-F2A进行连接,得到融合基因,将该融合基因构建于慢病毒载体中;
所述Furin-linker-spacer-F2A的核苷酸序列如SEQ ID NO.4所示。
3.根据权利要求2所述的慢病毒载体,其特征在于,表达靶向CD19和CD20的CAR的核苷酸序列如SEQ ID NO.2所示;表达PD1-CD28嵌合受体的核苷酸序列如SEQ ID NO.7所示。
4.根据权利要求2或3所述的慢病毒载体,其特征在于,在所述融合基因的上游插入启动子,所述启动子为在T细胞内高效表达的启动子。
5.根据权利要求4所述的慢病毒载体,其特征在于,所述启动子为启动子EF1α。
6.根据权利要求5所述的慢病毒载体,其特征在于,所述启动子在所述融合基因上游308~519bp处。
7.根据权利要求1~3任一项所述的慢病毒载体,其特征在于,所述慢病毒载体选自启动子为EF1α的慢病毒载体。
8.权利要求1~7任一项所述的慢病毒载体在制备抗肿瘤药物中的应用。
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CN108841792A (zh) * | 2018-06-14 | 2018-11-20 | 浙江大学 | 靶向cd19和ebna1基因修饰的t细胞及其制备方法与应用 |
CN110724697B (zh) * | 2018-07-16 | 2023-10-03 | 上海恒润达生生物科技股份有限公司 | 靶向gpc3和cd19双靶点的嵌合抗原受体方法和用途 |
CN110981971B (zh) * | 2019-12-25 | 2022-12-16 | 华夏源(上海)细胞基因工程股份有限公司 | 一种靶向cd19和cd20的双靶点嵌合抗原受体及其表达载体和应用 |
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CN111549044B (zh) * | 2020-07-13 | 2020-10-23 | 北京市肿瘤防治研究所 | 靶向trbc1 car-t细胞的制备方法与应用 |
CN111944850B (zh) * | 2020-08-28 | 2023-03-31 | 澳门大学 | 表达抗cd22嵌合抗原受体和pd-l1阻断蛋白的细胞的制备方法、表达载体及应用 |
CN112266899A (zh) * | 2020-10-26 | 2021-01-26 | 北京卡替医疗技术有限公司 | 修饰的免疫细胞及其用途 |
CN113234685A (zh) * | 2021-05-25 | 2021-08-10 | 临沂大学 | 一种双靶点cd19/cd20联用嵌合抗原受体t细胞及其制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103965361A (zh) * | 2013-02-06 | 2014-08-06 | 上海细胞治疗工程技术研究中心有限公司 | 一种t细胞信号的嵌合分子转换器及其用途 |
CN104114233A (zh) * | 2011-07-29 | 2014-10-22 | 宾夕法尼亚大学董事会 | 转换共刺激受体 |
CN106795217A (zh) * | 2014-07-24 | 2017-05-31 | 蓝鸟生物公司 | Bcma嵌合抗原受体 |
CN107106665A (zh) * | 2014-06-06 | 2017-08-29 | 纪念斯隆-凯特琳癌症中心 | 靶向间皮素的嵌合抗原受体及其用途 |
-
2017
- 2017-12-07 CN CN201711288511.8A patent/CN108085340B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104114233A (zh) * | 2011-07-29 | 2014-10-22 | 宾夕法尼亚大学董事会 | 转换共刺激受体 |
CN103965361A (zh) * | 2013-02-06 | 2014-08-06 | 上海细胞治疗工程技术研究中心有限公司 | 一种t细胞信号的嵌合分子转换器及其用途 |
CN107106665A (zh) * | 2014-06-06 | 2017-08-29 | 纪念斯隆-凯特琳癌症中心 | 靶向间皮素的嵌合抗原受体及其用途 |
CN106795217A (zh) * | 2014-07-24 | 2017-05-31 | 蓝鸟生物公司 | Bcma嵌合抗原受体 |
Non-Patent Citations (2)
Title |
---|
Increasing the safety and efficacy of chimeric antigen receptor T cell therapy;Hua Li and YB Zhao;《Protein&Cell》;20170422;第8卷;第573-589页 * |
Redirected Primary Human Chimeric Antigen Receptor natural Killer Cells As an "Off-the-Shelf immunotherapy" for improvement in Cancer Treatment;Olaf Oberschmidt等;《frontiers in Immunology》;20170609;第8卷;第1-9页 * |
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