CN113382741A - Car t细胞方法和构建体 - Google Patents
Car t细胞方法和构建体 Download PDFInfo
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Abstract
本公开内容提供了用于过继细胞疗法的非复制病毒载体(RNV)。所述RNV可以在体内向免疫细胞(例如，T‑细胞)递送嵌合抗原受体。
Description
相关申请的交叉引用
本申请根据美国法典第35篇第119条要求2019年1月6日提交的美国临时申请系列号62/788,894的优先权，其公开内容通过引用并入本文。
技术领域
本公开内容提供了用于过继细胞疗法的复制病毒载体(RRV)和非复制病毒载体(RNV)。RRV和RNV可以在体内将嵌合抗原受体递送给免疫细胞(例如，T-细胞)。
序列表的通过引用并入
伴随该文件的是序列表，其标题为“Sequence-Listing_ST25.txt”，创建于2020年1月6日，且具有172,643字节的数据，在IBM-PC、MS-Windows操作系统上进行了机器格式化。出于所有目的，序列表特此通过引用整体并入本文。
背景
在2013年，Science杂志将癌症免疫疗法称为“年度突破”(J.Couzan-Frankel,Science,342:1432-1433,2013)。嵌合抗原受体(CAR)工程改造的T细胞(June&Sadelain,NEngl J Med,379:64-73,2018)是这一称号的关键部分，至少两组研究人员在2013年开始用“许多白血病消失(pounds of leukemia that melted away)”来报道患者中对CAR疗法的吸引眼球的应答，并显示从晚期癌症中的惊人恢复。CAR是工程改造的受体，其将定义的特异性移植到增强T细胞功能的免疫效应细胞(通常为T细胞)上。最近，这种疗法的两种形式，即Kymriah(也被称作tisagenlecleucel,[www.]hcp.novartis.com/products/kymriah/，由Novartis销售)和Yeskarta(也被称作axicabtagene ciloleucel,[www.]yescartahcp.com，由Kite Pharmaceuticals开发，现在由Gilead销售)，已被批准用于各种类型的B细胞白血病的商业销售，这代表着个性化医学的突破。在该策略中，将患者自身的T淋巴细胞收获、离体培养并进行基因修饰以编码结合肿瘤抗原的合成受体，从而使T细胞在重新输注入患者体内后识别并杀死表达抗原的癌细胞。如上面所指出的，该方案已被批准用于识别B细胞标志物CD19的CAR(S.L.Maude等人,N Engl J Med.,371:1507-17,2014)，并已经在临床上证明了对于CD20和BCMA(各种类型的淋巴瘤以及一些类型的正常B细胞的标志物)的成功，缺乏它们的患者可以通过输注γ-球蛋白来简单治疗。现在正在积极努力使用这些类型的针对实体瘤的疗法(K.B.Long等人,Front.Immunol.,2018,[https://]doi.org/10.3389/fimmu.2018.02740；K.Ullah等人,Oncol.Reports,2018；[https://]doi.org/10.3892/or.2018.6758)；修饰不同的群体，诸如CD34+造血干细胞、γδT细胞和NK细胞；使用血液/骨髓、脾细胞的其它类型的基因修饰来达到抗癌、抗病毒和其它类型的治疗效果。一个好实例是CD34+造血干细胞，在欧洲有一种被批准的疗法(StrimvelisTM，由GlaxoSmithKline开发，现在由Orchard Therapeutics销售)用于治疗患有遗传性疾病X-连锁重症联合免疫缺陷综合征(X-SCIDS)的儿童。这些方法中的绝大多数涉及患者细胞的离体分离、易感细胞群体的基因修饰和再植入。该策略的最早实例之一是ADA-SCIDS患者的部分成功治疗(R.M.Blaese,Immunol.Res.,38:274-284,2007；DOI 10.1007/s12026-007-0009-z)，并尝试治疗供体淋巴细胞输注后的移植物抗宿主病，作为同种异体骨髓移植治疗的一部分(G.Bonini,Science,276:1719-1724,1997)。所有这些程序都涉及用逆转录病毒载体、慢病毒载体或其它基因转移方法对患者T细胞进行离体基因修饰，然后重新输注经修饰的细胞。
以上讨论的疗法全部用离体细胞制剂进行，通常用自体组织进行。该方案有几个原因：首先，所使用的基因转移剂不是非常有效，并且只能通过将它们与部分地或完全地纯化的制剂一起使用来转导靶细胞；其次，注射的基因转移载体，特别是整合载体，被认为具有插入诱变的潜在风险，因为这样的程序已导致一些免疫抑制的个体(例如X-SCIDS患者)中的淋巴瘤；第三，从离体制备细胞的过程中更容易鉴定异常细胞或其它异常的观点来看，离体方案也被认为是更安全的。该离体转导策略已被证明是以下方面的极端限制因素：疗法可用性：成本；和一致性([https://]xtalks.com/kymriah-manufacturing-issues-spell-trouble-for-commercial ization-of-novartis-car-t-therapy-1475/,[https://]labiotech.eu/medical/kymriah-car-t-therapy-novartis-sales/)。离体方案的其它缺点是起始材料的变化，其导致预测性和成功时机的缺乏，为每位患者制备新鲜产品的程序极其费力和昂贵，并且在大多数情况下需要创建“空间”用于通过消融患者体内的现有细胞群体成功地进行最终再植入(例如，S.L.Maude等人,N Engl J Med.,378:439-448,2018；doi:10.1056/NEJMoa1709866)。已经提出使用经工程改造的同种异体的T细胞作为解决方案，并且已经开始临床试验，但是这种权宜方法伴有几个问题。首先，除了同卵双胞胎之间，基本上没有完美的HLA匹配，因此CAR T细胞将可能被同种异体应答缩短寿命和消除；使用已去除HLA的细胞的尝试增加源自CAR T细胞的白血病的风险。其次，尽管该方法可能用同种异体的CAR T细胞的特定制品治疗超过一名患者，但估计可以治疗的最大患者人数为约100名；那么就需要制备未知效能的新鲜制品并在体外进行测试，这可能对于体内效能预测而言是非常误导性的。
发明内容
本公开内容通过使用直接转导患者细胞的编码治疗基因的整合基因转移载体的直接施用，提供了解决这些困难中的至少一些的方法。在一个实施方案中，所述载体是逆转录病毒载体，所述靶标是T细胞，且所述转基因是CAR或类似的人工受体构建体(例如，第一代、第二代、第三代等CAR构建体)。在另一个实施方案中，所述载体是逆转录病毒载体，所述靶标是已经通过施用外部试剂活化的细胞，并且所述转基因编码治疗活性。在该实施方案和其它实施方案中，逆转录病毒载体可以是复制型(RRV)或非复制型(RNV)，并且可以衍生自任何整合病毒，诸如泡沫病毒、慢病毒、α、β或γ逆转录病毒或CRISPR元件，并且也包括非病毒整合载体，诸如基于转座子的那些诸如“Piggy-bac”(Saito等人,Cytother.16:1257-1269,2014)或“睡美人(Sleeping Beauty)”。在另一个实施方案中，所述载体是逆转录病毒载体，所述活化剂是粒细胞集落刺激因子(GCSF)，且所述靶标是CD34+细胞。在另一个实施方案中，所述载体是γ逆转录病毒非复制载体，所述靶群体是天然地活化的T细胞，且所述转基因是T细胞受体。在另一个实施方案中，所述载体是γ逆转录病毒载体，所述靶细胞群体是天然地活化的细胞群体，且所述转基因编码免疫活化剂。在另一个实施方案中，所述载体是γ逆转录病毒载体，所述靶群体是天然地活化的T细胞，且所述转基因是CAR(例如，第一、第二、第三代CAR)。在另一个实施方案中，所述CAR包含靶向以下中一种或多种的结合结构域：CD5；CD19；CD123；CD22；CD30；CD171；CS1(也被称作CD2子集1、CRACC、SLAMF7、CD319和19A24)；C-型凝集素-样分子-1(CLL-1或CLECL1)；CD33；表皮生长因子受体变体III(EGFRviii)；神经节苷脂G2(GD2)；神经节苷脂GD3(aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer)；TNF受体家族成员B细胞成熟(BCMA)；Tn抗原((Tn Ag)或(GalNAcα-Ser/Thr))；前列腺特异性的膜抗原(PSMA)；受体酪氨酸激酶-样孤儿受体1(ROR1)；Fms样酪氨酸激酶3(FLT3)；肿瘤相关的糖蛋白72(TAG72)；CD38；CD44v6；在急性白血病或淋巴瘤上表达、但不在造血祖细胞上表达的糖基化的CD43表位，在非造血癌上表达的糖基化的CD43表位，癌胚抗原(CEA)；上皮细胞粘附分子(EPCAM)；B7H3(CD276)；KIT(CD117)；白介素-13受体亚基α-2(IL-13Ra2或CD213A2)；间皮素；白介素11受体α(IL-llRa)；前列腺干细胞抗原(PSCA)；蛋白酶丝氨酸21(睾蛋白或PRSS21)；血管内皮生长因子受体2(VEGFR2)；Lewis(Y)抗原；CD24；血小板-衍生的生长因子受体β(PDGFR-β)；阶段特异性的胚胎抗原-4(SSEA-4)；CD20；叶酸盐受体α(FRa或FR1)；叶酸盐受体β(FRb)；受体酪氨酸-蛋白激酶ERBB2(Her2/neu)；细胞表面相关的粘蛋白1(MUC1)；表皮生长因子受体(EGFR)；神经细胞粘附分子(NCAM)；前列腺酶；前列腺酸性磷酸酶(PAP)；突变的延伸因子2(ELF2M)；Ephrin B2；成纤维细胞活化蛋白α(FAP)；胰岛素-样生长因子1受体(IGF-I受体),碳酸酐酶IX(CAlX)；蛋白酶体(Prosome,Macropain)亚基,β类型,9(LMP2)；糖蛋白100(gpl00)；由裂点簇区(BCR)和Abelson鼠白血病病毒癌基因同系物1(Abl)组成的癌基因融合蛋白(bcr-abl)；酪氨酸酶；ephrin A型受体2(EphA2)；唾液酸基Lewis粘附分子(sLe)；神经节苷脂GM3(aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(l-1)Cer)；转谷氨酰胺酶5(TGS5)；高分子量-黑素瘤相关抗原(HMWMAA)；o-乙酰基-GD2神经节苷脂(OAcGD2)；肿瘤内皮标志物1(TEM1/CD248)；肿瘤内皮标志物7相关的(TEM7R)；封闭蛋白6(CLDN6)；促甲状腺激素受体(TSHR)；G蛋白偶联受体C类5组,成员D(GPRC5D)；染色体X开放读码框61(CXORF61)；CD97；CD179a；间变性淋巴瘤激酶(ALK)；聚唾液酸；胎盘特异性的1(PLAC1)；globoH糖神经酰胺的己糖部分(GloboH)；乳腺分化抗原(NY-BR-1)；uroplakin 2(UPK2)；甲型肝炎病毒细胞受体1(HAVCR1)；肾上腺素受体β3(ADRB3)；pannexin 3(PANX3)；G蛋白偶联受体20(GPR20)；淋巴细胞抗原6复合物,基因座K9(LY6K)；嗅觉受体51E2(OR51E2)；TCRγ交替读码框蛋白(TARP)；肾母细胞瘤蛋白(WT1)；癌症/睾丸抗原1(NY-ES0-1)；癌症/睾丸抗原2(LAGE-1a)；黑素瘤相关抗原1(MAGE-A1)；位于染色体12p上的ETS易位-变体基因6(ETV6-AML)；精子蛋白17(SPA17)；X抗原家族,成员lA(XAGEl)；结合血管生成素的细胞表面受体2(Tie 2)；黑素瘤癌症睾丸抗原-1(MAD-CT-1)；黑素瘤癌症睾丸抗原-2(MAD-CT-2)；Fos相关抗原1；肿瘤蛋白p53(p53)；p53突变体；prostein；存活素；端粒末端转移酶；前列腺癌肿瘤抗原-1(PCT A-1或半乳糖凝集素8),被T细胞1识别的黑素瘤抗原(MelanA或MARTI)；大鼠肉瘤(Ras)突变体；人端粒末端转移酶逆转录酶(hTERT)；肉瘤易位断点；细胞凋亡的黑素瘤抑制剂(ML-IAP)；ERG(跨膜蛋白酶,丝氨酸2(TMPRSS2)ETS融合基因)；N-乙酰基葡糖胺基-转移酶V(NA17)；成对的盒蛋白Pax-3(PAX3)；雄激素受体；细胞周期蛋白Bl；v-myc禽髓细胞瘤病病毒癌基因神经母细胞瘤衍生的同系物(MYCN)；Ras同系物家族成员C(RhoC)；酪氨酸酶相关蛋白2(TRP-2)；细胞色素P450lB 1(CYPlB 1)；CCCTC-结合因子(锌指蛋白)-样(BORIS或印迹位点的调节剂的同系物),被T细胞3识别的鳞状细胞癌抗原(SART3)；成对的盒蛋白Pax-5(PAX5)；顶体蛋白原结合蛋白sp32(OY-TESl)；淋巴细胞特异性的蛋白酪氨酸激酶(LCK)；A激酶锚蛋白4(AKAP-4)；滑膜肉瘤,X断点2(SSX2)；高级糖化终产物的受体(RAGE-1)；肾遍布物1(RUl)；肾遍布物2(RU2)；legumain；人乳头瘤病毒E6(HPV E6)；人乳头瘤病毒E7(HPV E7)；肠羧基酯酶；突变的热激蛋白70-2(mut hsp70-2)；CD79a；CD79b；CD72；白细胞-相关的免疫球蛋白-样受体1(LAIRl)；IgA受体的Fc片段(FCAR或CD89)；白细胞免疫球蛋白-样受体亚家族A成员2(LILRA2)；CD300分子-样家族成员f(CD300LF)；C-型凝集素结构域家族12成员A(CLEC12A)；骨髓间质细胞抗原2(BST2)；含有EGF-样模块的粘蛋白-样激素受体-样2(EMR2)；淋巴细胞抗原75(LY75)；磷脂酰肌醇蛋白聚糖-3(GPC3)；Fc受体-样5(FCRL5)；和免疫球蛋白λ-样多肽1(IGLLl),MPL,生物素,c-MYC表位标签,CD34,LAMP1 TROP2,GFRα4,CDH17,CDH6,NYBR1,CDH19,CD200R,Slea(CA19.9；唾液酸基Lewis抗原)；岩藻糖基-GM1,PTK7,gpNMB,CDH1-CD324,DLL3,CD276/B7H3,IL11Ra,IL13Ra2,CD179b-IGLl1,TCRγ-δ,NKG2D,CD32(FCGR2A),Tn ag,Tim1-/HVCR1,CSF2RA(GM-CSFR-α),TGFβR2,Lews Ag,TCR-β1链,TCR-β2链,TCR-γ链,TCR-δ链,FITC,促黄体激素受体(LHR),促卵泡激素受体(FSHR),促性腺素激素受体(CGHR或GR),CCR4,GD3,SLAMF6,SLAMF4,HIV1包膜糖蛋白,HTLV1-Tax,CMV pp65,EBV-EBNA3c,KSHV K8.1,KSHV-gH,甲型流感血凝素(HA),GAD,PDL1,鸟苷酸环化酶C(GCC),针对桥粒核心糖蛋白3(Dsg3)的自身抗体,针对桥粒核心糖蛋白1(Dsg1)的自身抗体,HLA,HLA-A,HLA-A2,HLA-B,HLA-C,HLA-DP,HLA-DM,HLA-DOA,HLA-DOB,HLA-DQ,HLA-DR,HLA-G,IgE,CD99,Ras G12V,组织因子1(TF1),AFP,GPRC5D,封闭蛋白18.2(CLD18A2或CLDN18A.2)),P-糖蛋白,STEAP1,Liv1,连接素-4,Cripto,gpA33,BST1/CD157,低电导氯离子通道,和被TNT抗体识别的抗原。
附图说明
图1显示了本公开内容的质粒构建体的序列和序列注解。
图2显示了病毒RNA(vRNA)序列，其中多克隆位点突出显示/为粗体/标有下划线。可以将CAR编码序列(RNA)克隆进多克隆位点(MCS)中以形成RNVCAR病毒序列。
图3显示了用于例证本发明的各种编码CAR的DNA序列。应当指出，涵盖对应的RNA序列，其中在序列中用U替换T。
图4显示了用于生产CD19-RNVCAR的各种质粒序列，其含有结合CD19的scFv序列。
图5A-B示意地描绘了本公开内容的示例性RNV载体。
图6是在RNV-GFP的第一个静脉内剂量后7天在外周血单核细胞(PBMC)中确定的具有RNV-GFP的Balb/c小鼠中的PBMC中的感染水平的图。
图7显示了在用于产生图6的数据的平行样品中的在以下PBMC群体的子集中评价的RNV-GFP感染的图：CD11b+、CD4+、CD8+和CD19+。
图8显示了A20 B-细胞淋巴瘤动物模型中的实验的结果，其中从A20植入后第5天开始，以每天1E7或1E8 TU的剂量给荷瘤小鼠静脉内注射载体RNV-1D3CAR连续5天。监测小鼠37天并评估存活率。与媒介物处理的对照组(无RNV)或较低剂量的RNV-1D3CAR(5E7)相比，较高剂量的RNV-1D3CAR(5E8 TU)导致A20淋巴瘤荷瘤小鼠中存活率的改善。
具体实施方式
如在本文中和在所附权利要求书中所使用的，单数形式“一个/种(a)”、“一个/种(an)”和“该/所述”包括复数指示物，除非上下文另外清楚地指明。因而，例如，对“一个细胞”的提及包括多个这样的细胞，且对“所述多核苷酸”的提及包括对一种或多种多核苷酸的提及，诸如此类。
并且，除非另外说明，“或”的使用是指“和/或”。类似地，“包含(comprise)”、“包含(comprises)”、“包含(comprising)”、“包括(include)”、“包括(includes)”和“包括(including)”是可互换的，并不旨在进行限制。
还应当理解，在各个实施方案的描述使用术语“包含”的情况下，本领域技术人员会理解，在一些具体情况下，可以可替换地使用语言“基本上由……组成”或“由……组成”描述一个实施方案。
除非另有定义，否则本文使用的所有技术和科学术语具有本发明所属领域的普通技术人员所通常理解的相同含义。Allen等人,Remington:The Science and Practice ofPharmacy第22版,Pharmaceutical Press(2012年9月15日)；Hornyak等人,Introductionto Nanoscience and Nanotechnology,CRC Press(2008)；Singleton和Sainsbury,Dictionary of Microbiology and Molecular Biology第3版,修订版,J.Wiley&Sons(NewYork,NY 2006)；Smith,March’s Advanced Organic Chemistry Reactions,Mechanismsand Structure第7版,J.Wiley&Sons(New York,NY 2013)；Singleton,Dictionary of DNAand Genome Technology第3版,Wiley-Blackwell(2012年11月28日)；和Green和Sambrook,Molecular Cloning:A Laboratory Manual第4版,Cold Spring Harbor LaboratoryPress(Cold Spring Harbor,NY 2012),给本领域技术人员提供了在本申请中使用的许多术语的一般指导。关于如何制备抗体的参考文献，参见Greenfield,Antibodies ALaboratory Manual第2版,Cold Spring Harbor Press(Cold Spring Harbor NY,2013)；
和Milstein,Derivation of specific antibody-producing tissue cultureand tumor lines by cell fusion,Eur.J.Immunol.1976年7月,6(7):511-9；Queen和Selick,Humanized immunoglobulins,美国专利号5,585,089(1996年12月)；和Riechmann等人,Reshaping human antibodies for therapy,Nature 1988年3月24日,332(6162):323-7。可替换地，商业供应商可以制备和提供单克隆抗体或其它结合分子以提供CAR的T细胞活化分子的结合部分。本文提供的所有标题和副标题仅仅为了容易阅读，且不应解释为限制本发明。尽管与本文描述的那些类似或等同的方法和材料可以用于本发明的实践或测试，但是在下面描述了合适的方法和材料。在本文中提及的所有出版物、专利申请、专利和其它参考文献通过引用整体并入。在冲突的情况下，以本说明书(包括定义)为准。另外，材料、方法和具体实例仅仅是示例性的且不意图是限制性的。
本公开内容提供了用于过继细胞疗法的药物制品、载体、细胞和方法。本公开内容的载体包含复制型或非复制型病毒衍生的载体，其包含各种嵌合抗原受体的编码序列。
当涉及可测量值诸如量、时间持续时间等时，术语“约”意在涵盖从指定值的±20％的变化，或在一些情况下±10％，或在一些情况下±5％，或在一些情况下±1％，或在一些情况下±0.1％，因为这样的变化对于执行公开的方法或描述本文中的组合物是适当的。此外，任何值或范围(例如，小于20或类似的术语)明确地包括在这样的值之间或直到所述值的任意整数。因而，例如，“1-5个突变”明确地包括1、2、3、4和/或5个突变。
术语“抗原结合分子”(ABM)表示对靶抗原具有特异性亲和力的任何分子，如在结合测定诸如ELISA中所证实的。它包括抗体、抗体片段、骆驼科或鲨鱼或其它非典型结构化抗体，且还包括宽范围的抗体置换物或替代物，诸如非免疫球蛋白(Ig)支架蛋白。这样的分子已经使用随机化策略为生物治疗剂开发以鉴定抗原结合序列(U.H Wiedle等人.CancerGenomics&Proteomics 10:155-168,2013；K.Skrlec等人.Trends in Biotechnology,33:408-418,2015)。非-Ig支架蛋白是来自人类和其它物种的天然蛋白的结构域衍生亚基，或者是人工的，并且其大小范围为6-20kDa，且可以从单个多肽表达。它们在α-螺旋或β折叠框架中具有表面暴露的环或氨基酸，其可耐受插入、缺失和置换，所述插入、缺失和置换通过随机化、噬菌体展示筛选和亲和力成熟过程产生可作为拮抗剂或激动剂发挥功能的抗原结合支架蛋白。迄今为止，已经鉴定出并开发了超过50种不同类别的非-Ig支架蛋白用于作为支架结合剂的治疗剂。由于它们的大小，这些蛋白面临的一个主要挑战是快速的肾脏清除，从而导致在循环中的半衰期短，但是当将它们并入CAR或其它膜穿透分子中时，这不是问题。
另一个挑战是，它们经常具有比单克隆抗体更低的结合亲和力(KD1-100nM)，并且与快速解离速率有关。这些支架蛋白的包括二聚化结构域的基因修饰可能增加空间位阻介导的阻断或亲合力，因此在某些信号传导途径中，这可以导致生物学功能和治疗效果。已经提出了多种方法，并且至少部分地使用包含支架蛋白的融合蛋白进行了测试。
本公开内容提供了使用结合结构域的组合物和方法，所述结合结构域包含通过支架结构域连接的重链和/或轻链CDR的组合(例如，Adhiron支架；来自人stefin A的支架-参见，EP22792058B1和WO2019/008335，其公开内容通过引用并入本文)。表1和2提供了可用于本公开内容的组合物和方法的序列。请注意，在下面的核酸序列中“T”可以是“U”，因为涵盖RNA。
表1:一些可以作为抗原结合蛋白发挥功能的非-Ig支架蛋白的氨基酸序列：
表2:可以作为抗原结合蛋白发挥功能的非-Ig支架蛋白的核酸序列:
本公开内容提供了可以递送给细胞或直接递送给受试者的病毒载体，其含有编码例如具有抗原结合结构域(例如，抗体或抗体片段；或非抗体结合结构域诸如非免疫球蛋白(Ig)支架蛋白或编码序列的组合等)的CAR的异源多核苷酸。所述病毒载体可以是腺病毒载体、麻疹载体、疱疹载体、逆转录病毒载体(包括α-、β-、γ-、δ-逆转录病毒载体、泡沫病毒载体诸如猿猴泡沫病毒(SFV)或人泡沫病毒(HFV)或慢病毒载体)、杆状病毒载体诸如水疱性口炎病毒载体、里奥病毒载体、Seneca Valley病毒载体、痘病毒载体(包括动物痘或牛痘衍生的载体)、细小病毒载体(包括AAV载体)、甲病毒载体或本领域技术人员已知的其它病毒载体(也参见，例如，Concepts in Genetic Medicine,Boro Dropulic和Barrie Carter编,Wiley,2008,Hoboken,NJ.；The Development of Human Gene Therapy,TheodoreFriedmann编,Cold Springs Harbor Laboratory Press,Cold springs Harbor,NewYork,1999；Gene and Cell Therapy,Nancy Smyth Templeton编,Marcel Dekker Inc.,New York,New York,2000和Gene&Cell Therapy:Therapeutic Mechanism andStrategies,第3版,Nancy Smyth Templetone编,CRC Press,Boca Raton,FL,2008；其公开内容通过引用并入本文)。
如下面和上面所述，本公开内容的逆转录病毒载体可以衍生自(即，亲本核苷酸序列获得自)MLV、MoMLV、GALV、FELV、HIV等，且被工程改造成含有编码CAR或CAR-样-肽的序列，其中常规scFv抗原结合结构域被直接置换或通过接头被另一类抗原结合结构域置换，使得在用这样的载体转导且表达CAR或CAR-样蛋白的细胞中，在膜嵌入的CAR-样分子的另一端处的ζ链在抗原结合后造成细胞活化。在这里，其它类型的抗原结合结构域可以是另一种scFv或抗体片段或非-Ig-分子诸如本文所述(例如adenectin、pronectin、affimer、hckamer或anti-calin)。
本文中使用的术语“抗体”表示从与抗原特异性地结合的免疫球蛋白分子衍生出的蛋白或多肽序列。抗体可以是单克隆的、或多克隆的、多链或单链、或完整的免疫球蛋白，且可以衍生自天然来源或重组来源。抗体可以是免疫球蛋白分子的四聚体。抗体可以是‘人源化的’、‘嵌合的’或非-人的。
术语“抗体片段”表示抗体的至少一个部分，其保留与抗原的表位特异性地相互作用(例如，通过结合、空间位阻、稳定/去稳定、空间分布)的能力。抗体片段的实例包括，但不限于：Fab、Fab'、F(ab'h、Fv片段、scFv抗体片段、二硫化物连接的Fvs(sdFv)、由VH和CHl结构域组成的Fd片段、直链抗体、单结构域抗体诸如sdAb(vL或vH)、骆驼科vHH结构域、由抗体片段形成的多特异性抗体诸如包含通过铰链区的二硫键连接的2个Fab片段的二价片段、和分离的CDR或抗体的其它表位结合片段。还可以将抗原结合片段并入单结构域抗体、大抗体、微米抗体、纳米抗体、细胞内抗体、双体、三体、四体、v-NAR和二-scFv中(参见，例如，Hollinger和Hudson,Nature Biotechnology 23:1126-1136,2005)。还可以将抗原结合片段移植进基于多肽诸如纤连蛋白III型(Fn3)的支架中(参见美国专利号.:6,703,199，其描述了纤连蛋白多肽微米抗体)。
术语“抗体重链”表示以它们的天然存在的构象存在于抗体分子中的两类多肽链中的较大者，且其通常决定抗体所属的类别。
术语“抗体轻链”表示以它们的天然存在的构象存在于抗体分子中的两类多肽链中的较小者。Kappa(κ)和lamda(λ)轻链表示两种主要抗体轻链同种型。
术语“抗癌效应”表示可以通过多种方式表现出来的生物学效应，包括、但不限于肿瘤体积的减小，癌细胞数量的减少，转移灶数量的减少，预期寿命的增加，癌细胞增殖的减少，癌细胞存活期的减少，或与癌性病况相关的各种生理学症状的改善。
“抗癌剂”表示抑制异常的细胞分裂和生长、抑制赘生性细胞的迁移、抑制侵袭力或防止癌症生长和转移的药剂。该术语包括化学治疗剂、生物剂(例如，siRNA、病毒载体诸如经工程改造的MLV、腺病毒、递送细胞毒性基因的疱疹病毒)、抗体等。
术语“抗原”或“Ag”表示引起免疫应答的分子。该免疫应答可能涉及抗体产生，或特定有免疫学能力细胞的活化，或两者。熟练的技术人员会理解，任何大分子(包括基本上所有的蛋白或肽)都可以充当抗原。此外，抗原可以衍生自重组或基因组DNA。熟练的技术人员会理解，在本文中使用这样的任何DNA：其包含编码引发免疫应答的蛋白的核苷酸序列或部分核苷酸序列，因此编码“抗原”作为该术语。此外，本领域技术人员会理解，抗原不需要仅由基因的全长核苷酸序列编码。显而易见的是，本公开内容包括、但不限于使用超过一个基因的部分核苷酸序列，并且这些核苷酸序列以各种组合排列以编码引发期望的免疫应答的多肽。此外，熟练的技术人员会理解，抗原根本不需要由“基因”编码。显而易见的是，抗原可以合成产生或可以源自生物样品，或者可能是除多肽以外的大分子。这样的生物样品可以包括、但不限于组织样品、肿瘤样品、细胞或具有其它生物组分的流体。
靶抗原的非限制性实例包括：CD5、CD19；CD123；CD22；CD30；CD171；CS1(也被称作CD2子集1、CRACC、SLAMF7、CD319和19A24)；C-型凝集素-样分子-1(CLL-1或CLECL1)；CD33；表皮生长因子受体变体III(EGFRviii)；神经节苷脂G2(GD2)；神经节苷脂GD3(aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer)；TNF受体家族成员B细胞成熟(BCMA)；Tn抗原((Tn Ag)或(GalNAcα-Ser/Thr))；前列腺特异性的膜抗原(PSMA)；受体酪氨酸激酶-样孤儿受体1(ROR1)；Fms样酪氨酸激酶3(FLT3)；肿瘤相关的糖蛋白72(TAG72)；CD38；CD44v6；在急性白血病或淋巴瘤上表达、但不在造血祖细胞上表达的糖基化的CD43表位，在非造血癌上表达的糖基化的CD43表位，癌胚抗原(CEA)；上皮细胞粘附分子(EPCAM)；B7H3(CD276)；KIT(CD117)；白介素-13受体亚基α-2(IL-13Ra2或CD213A2)；间皮素；白介素11受体α(IL-llRa)；前列腺干细胞抗原(PSCA)；蛋白酶丝氨酸21(睾蛋白或PRSS21)；血管内皮生长因子受体2(VEGFR2)；Lewis(Y)抗原；CD24；血小板-衍生的生长因子受体β(PDGFR-β)；阶段特异性的胚胎抗原-4(SSEA-4)；CD20；叶酸盐受体α(FRa或FR1)；叶酸盐受体β(FRb)；受体酪氨酸-蛋白激酶ERBB2(Her2/neu)；细胞表面相关的粘蛋白1(MUC1)；表皮生长因子受体(EGFR)；神经细胞粘附分子(NCAM)；前列腺酶；前列腺酸性磷酸酶(PAP)；突变的延伸因子2(ELF2M)；Ephrin B2；成纤维细胞活化蛋白α(FAP)；胰岛素-样生长因子1受体(IGF-I受体),碳酸酐酶IX(CAlX)；蛋白酶体(Prosome,Macropain)亚基,β类型,9(LMP2)；糖蛋白100(gpl00)；由裂点簇区(BCR)和Abelson鼠白血病病毒癌基因同系物1(Abl)组成的癌基因融合蛋白(bcr-abl)；酪氨酸酶；ephrin A型受体2(EphA2)；唾液酸基Lewis粘附分子(sLe)；神经节苷脂GM3(aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(l-1)Cer)；转谷氨酰胺酶5(TGS5)；高分子量-黑素瘤相关抗原(HMWMAA)；o-乙酰基-GD2神经节苷脂(OAcGD2)；肿瘤内皮标志物1(TEM1/CD248)；肿瘤内皮标志物7相关的(TEM7R)；封闭蛋白6(CLDN6)；促甲状腺激素受体(TSHR)；G蛋白偶联受体C类5组,成员D(GPRC5D)；染色体X开放读码框61(CXORF61)；CD97；CD179a；间变性淋巴瘤激酶(ALK)；聚唾液酸；胎盘特异性的1(PLAC1)；globoH糖神经酰胺的己糖部分(GloboH)；乳腺分化抗原(NY-BR-1)；uroplakin 2(UPK2)；甲型肝炎病毒细胞受体1(HAVCR1)；肾上腺素受体β3(ADRB3)；pannexin 3(PANX3)；G蛋白偶联受体20(GPR20)；淋巴细胞抗原6复合物,基因座K 9(LY6K)；嗅觉受体51E2(OR51E2)；TCRγ交替读码框蛋白(TARP)；肾母细胞瘤蛋白(WT1)；癌症/睾丸抗原1(NY-ES0-1)；癌症/睾丸抗原2(LAGE-1a)；黑素瘤相关抗原1(MAGE-A1)；位于染色体12p上的ETS易位-变体基因6(ETV6-AML)；精子蛋白17(SPA17)；X抗原家族,成员lA(XAGEl)；结合血管生成素的细胞表面受体2(Tie 2)；黑素瘤癌症睾丸抗原-1(MAD-CT-1)；黑素瘤癌症睾丸抗原-2(MAD-CT-2)；Fos相关抗原1；肿瘤蛋白p53(p53)；p53突变体；prostein；存活素；端粒末端转移酶；前列腺癌肿瘤抗原-1(PCT A-1或半乳糖凝集素8),被T细胞1识别的黑素瘤抗原(MelanA或MARTI)；大鼠肉瘤(Ras)突变体；人端粒末端转移酶逆转录酶(hTERT)；肉瘤易位断点；细胞凋亡的黑素瘤抑制剂(ML-IAP)；ERG(跨膜蛋白酶,丝氨酸2(TMPRSS2)ETS融合基因)；N-乙酰基葡糖胺基-转移酶V(NA17)；成对的盒蛋白Pax-3(PAX3)；雄激素受体；细胞周期蛋白Bl；v-myc禽髓细胞瘤病病毒癌基因神经母细胞瘤衍生的同系物(MYCN)；Ras同系物家族成员C(RhoC)；酪氨酸酶相关蛋白2(TRP-2)；细胞色素P450 lB 1(CYPlB 1)；CCCTC-结合因子(锌指蛋白)-样(BORIS或印迹位点的调节剂的同系物),被T细胞3识别的鳞状细胞癌抗原(SART3)；成对的盒蛋白Pax-5(PAX5)；顶体蛋白原结合蛋白sp32(OY-TESl)；淋巴细胞特异性的蛋白酪氨酸激酶(LCK)；A激酶锚蛋白4(AKAP-4)；滑膜肉瘤,X断点2(SSX2)；高级糖化终产物的受体(RAGE-1)；肾遍布物1(RUl)；肾遍布物2(RU2)；legumain；人乳头瘤病毒E6(HPV E6)；人乳头瘤病毒E7(HPVE7)；肠羧基酯酶；突变的热激蛋白70-2(mut hsp70-2)；CD79a；CD79b；CD72；白细胞-相关的免疫球蛋白-样受体1(LAIRl)；IgA受体的Fc片段(FCAR或CD89)；白细胞免疫球蛋白-样受体亚家族A成员2(LILRA2)；CD300分子-样家族成员f(CD300LF)；C-型凝集素结构域家族12成员A(CLEC12A)；骨髓间质细胞抗原2(BST2)；含有EGF-样模块的粘蛋白-样激素受体-样2(EMR2)；淋巴细胞抗原75(LY75)；磷脂酰肌醇蛋白聚糖-3(GPC3)；Fc受体-样5(FCRL5)；和免疫球蛋白λ-样多肽1(IGLLl),MPL,生物素,c-MYC表位标签,CD34,LAMP1 TROP2,GFRα4,CDH17,CDH6,NYBR1,CDH19,CD200R,Slea(CA19.9；唾液酸基Lewis抗原)；岩藻糖基-GM1,PTK7,gpNMB,CDH1-CD324,DLL3,CD276/B7H3,IL11Ra,IL13Ra2,CD179b-IGLl1,TCRγ-δ,NKG2D,CD32(FCGR2A),Tn ag,Tim1-/HVCR1,CSF2RA(GM-CSFR-α),TGFβR2,Lews Ag,TCR-β1链,TCR-β2链,TCR-γ链,TCR-δ链,FITC,促黄体激素受体(LHR),促卵泡激素受体(FSHR),促性腺素激素受体(CGHR或GR),CCR4,GD3,SLAMF6,SLAMF4,HIV1包膜糖蛋白,HTLV1-Tax,CMVpp65,EBV-EBNA3c,KSHV K8.1,KSHV-gH,甲型流感血凝素(HA),GAD,PDL1,鸟苷酸环化酶C(GCC),针对桥粒核心糖蛋白3(Dsg3)的自身抗体,针对桥粒核心糖蛋白1(Dsg1)的自身抗体,HLA,HLA-A,HLA-A2,HLA-B,HLA-C,HLA-DP,HLA-DM,HLA-DOA,HLA-DOB,HLA-DQ,HLA-DR,HLA-G,IgE,CD99,Ras G12V,组织因子1(TF1),AFP,GPRC5D,封闭蛋白18.2(CLD18A2或CLDN18A.2)),P-糖蛋白,STEAP1,Liv1,连接素-4,Cripto,gpA33,BST1/CD157,低电导氯离子通道,和被TNT抗体识别的抗原。
本文中使用的“亲和力”旨在描述结合强度的量度。在一些情况下，亲和力取决于结合剂与其靶标之间(例如，抗体与抗原(包括对结合结构域具有特异性的表位)之间)的立体化学配合的紧密度、它们之间接触面积的大小以及带电基团和疏水基团的分布。亲和力通常表示结合剂的结合其靶标的“能力”。在本领域中使用许多方法来测量“亲和力”。例如，用于计算抗体对抗原的亲和力的方法是本领域已知的，包括使用结合实验来计算亲和力。结合亲和力可以使用本领域已知的各种技术来确定，例如，表面等离振子共振、生物层干扰量度法、双极化干扰量度法、静态光散射、动态光散射、等温滴定量热法、ELISA、分析超速离心和流式细胞计量术。确定结合亲和力的一种示例性方法采用表面等离振子共振。表面等离振子共振是通过(例如使用BIAcore系统(Pharmacia Biosensor AB,Uppsala,Swedenand Piscataway,N.J.))检测生物传感器基质内的蛋白浓度的改变而允许分析实时生物特异性相互作用的光学现象。
“抗原结合结构域”表示由于其一级、二级或三级序列和/或翻译后修饰和/或电荷以高度特异性结合抗原的多肽或肽。抗原结合结构域可以源自不同的来源，例如，抗体、非免疫球蛋白结合蛋白诸如亲和体、affimer、DARPin或Pronectin(Skrlec等人,TrendsBiotechnol.,33:408-418,2015)、配体或受体。
“亲合力”表示结合剂与其靶标之间的相互作用的强度(例如，抗体与其抗原靶标、受体及其同源物之间等的相互作用的强度)。亲合力可以是弱的或强的。计算抗体对抗原的亲和力的方法是本领域已知的，包括使用结合实验来计算亲和力。在功能测定(例如，流式细胞计量术测定)中的抗体活性也反映了抗体亲和力。使用功能测定(例如，流式细胞计量术测定)可以在表型上表征和对比抗体和亲和力。
术语“缔合常数(Ka)”定义为受体与配体的缔合的平衡常数。
术语“自身抗原”表示刺激自身免疫应答的产生(例如自身抗体的产生)的内源性抗原。自身抗原还包括来自正常组织的自体抗原或抗原，其是细胞介导的或抗体介导的免疫应答的靶标，所述免疫应答可能导致自身免疫性疾病的发展。自身抗原的实例包括、但不限于桥粒核心糖蛋白1、桥粒核心糖蛋白3、及其片段。
本文中使用的“有益结果”可以包括、但绝不限于：减轻或缓解疾病状况的严重程度，防止疾病状况恶化，治愈疾病状况，防止疾病状况发展，降低患者发生疾病状况的机会，和延长患者的寿命或预期寿命。
本文中使用的术语“结合结构域”或“抗体分子”表示包含至少一个结构域(例如，与非特异性结构域相比可以以更高亲和力结合靶标的免疫球蛋白可变结构域序列)的蛋白，例如，免疫球蛋白链或其片段。该术语涵盖抗体和抗体片段以及其它非免疫球蛋白蛋白结合结构域(Skrlec等人,出处同上)。在另一个实施方案中，抗体分子是多特异性抗体分子，例如，它包含多个免疫球蛋白可变结构域序列，其中所述多个的第一个免疫球蛋白可变结构域序列具有对第一表位的结合特异性，且所述多个的第二个免疫球蛋白可变结构域序列具有对第二表位的结合特异性。在另一个实施方案中，多特异性抗体分子是双特异性抗体分子。双特异性抗体对两种抗原具有特异性。双特异性抗体分子的特征在于具有对第一表位的结合特异性的第一个免疫球蛋白可变结构域序列和具有对第二表位的结合特异性的第二个免疫球蛋白可变结构域序列。
“癌症”和“癌性的”表示或描述哺乳动物中通常以失调的细胞生长为特征的生理病况。癌症的实例包括、但不限于B-细胞淋巴瘤(霍奇金淋巴瘤和/或非霍奇金淋巴瘤)、T细胞淋巴瘤、骨髓瘤、骨髓增生异常综合征、皮肤癌、脑肿瘤、乳腺癌、结肠癌、直肠癌、食管癌、肛门癌、原发部位未知的癌症、内分泌癌、睾丸癌、肺癌、肝细胞癌、胃癌、胰腺癌、宫颈癌、卵巢癌、肝癌、膀胱癌、泌尿道的癌症、生殖器官的癌症、甲状腺癌、肾癌、癌、黑素瘤、头颈癌、脑癌(例如、多形性胶质母细胞瘤)、前列腺癌(包括、但不限于雄激素依赖性前列腺癌和非雄激素依赖性前列腺癌)和白血病。其它癌症和细胞增殖性病症将是在本领域中容易识别的。术语“肿瘤”和“癌症”在本文中可互换地使用，例如，两个术语都包括实体和液体肿瘤，例如，弥散的或循环的肿瘤。本文中使用的术语“癌症”或“肿瘤”包括恶化前的、以及恶性的癌症和肿瘤。
“化学治疗剂”是已知可用于癌症的化学疗法中的化合物。化学治疗剂的非限制性实例可以包括烷化剂诸如塞替派和
环磷酰胺；磺酸烷基酯诸如白消安、英丙舒凡和哌泊舒凡；氮丙啶类诸如苯佐替派(benzodopa)、卡波醌、美妥替派(meturedopa)和乌瑞替派(uredopa)；乙烯亚胺和甲基密胺，包括六甲蜜胺、三亚乙基密胺、三亚乙基磷酰胺、三亚乙基硫代磷酰胺和三羟甲基密胺；番荔枝内酯(acetogenin)(尤其是布拉他辛(bullatacin)和布拉他辛酮(bullatacinone))；喜树碱(包括合成的类似物托泊替康)；苔藓抑素；callystatin；CC-1065(包括它的合成类似物阿多来新、卡泽来新和比泽来新)；念珠藻环肽(尤其是念珠藻环肽1和念珠藻环肽8)；多拉司他汀；多卡米星(包括合成类似物KW-2189和CB1-TM1)；软珊瑚醇；水鬼蕉碱；sarcodictyin；海绵抑素；氮芥类诸如苯丁酸氮芥、萘氮芥、氯磷酰胺(cholophosphamide)、雌莫司汀、异环磷酰胺、氮芥、盐酸氧化氮芥、美法仑、新氮芥、苯芥胆甾醇、泼尼莫司汀、曲磷胺、乌拉莫司汀；硝基脲类诸如卡莫司汀、氯脲菌素、福莫司汀、洛莫司汀、尼莫司汀和雷莫司汀；抗生素类诸如烯二炔抗生素(例如卡奇霉素，尤其是卡奇霉素γ1I和卡奇霉素ωI1(参见，例如，Agnew,Chem.Intl.Ed.Engl.,33:183-186(1994))；达内霉素，包括达内霉素A；二膦酸盐类，诸如氯膦酸盐；埃斯波霉素；以及新制癌菌素生色团和有关的色蛋白烯二炔抗生素生色团)、阿克拉霉素(aclacinomysin)、放线菌素、氨茴霉素(authramycin)、偶氮丝氨酸、博来霉素、放线菌素C、carabicin、洋红霉素(caminomycin)、嗜癌霉素、色霉素、更生霉素、柔红霉素、地托比星、6-重氮基-5-氧代-L-正亮氨酸、
多柔比星(包括吗啉代-多柔比星、氰基吗啉代-多柔比星、2-吡咯啉代-多柔比星和脱氧多柔比星)、表柔比星、依索比星、伊达比星、麻西罗霉素、丝裂霉素类诸如丝裂霉素C、麦考酚酸、诺拉霉素、橄榄霉素、培洛霉素、泊非霉素(potfiromycin)、嘌罗霉素、三铁阿霉素、罗多比星、链黑霉素、链佐星、杀结核菌素、乌苯美司、净司他丁、佐柔比星；抗代谢药诸如甲氨蝶呤和5-氟尿嘧啶(5-FU)；叶酸类似物诸如二甲叶酸、甲氨蝶呤、蝶罗呤、三甲曲沙；嘌呤类似物诸如氟达拉滨、6-巯嘌呤、硫咪嘌呤、硫鸟嘌呤；嘧啶类似物诸如安西他滨、阿扎胞苷、6-氮杂尿苷、卡莫氟、阿糖胞苷、二脱氧尿苷、去氧氟尿苷、依诺他滨、氟尿苷；雄激素类诸如卡普睾酮、屈他雄酮丙酸盐、环硫雄醇、美雄烷、睾内酯；抗肾上腺类诸如氨鲁米特，米托坦，曲洛司坦；叶酸补充剂诸如亚叶酸(frolinic acid)；醋葡醛内酯；醛磷酰胺糖苷；氨基酮戊酸；恩尿嘧啶；安吖啶；bestrabucil；比生群；依达曲沙(edatraxate)；地磷酰胺(defofamine)；秋水仙胺；地吖醌；elformithine；依利醋铵；埃博霉素；依托格鲁；硝酸镓；羟基脲；香菇多糖；氯尼达明；美坦辛类诸如美坦辛和安丝菌素；米托胍腙；米托蒽醌；莫哌达醇；尼曲吖啶；喷司他丁；蛋氨氮芥；吡柔比星；洛索蒽醌；鬼臼酸；2-乙基酰肼；丙卡巴肼；
多糖复合物(JHS Natural Products,Eugene,Oreg.)；雷佐生；根霉素；西佐喃(sizofuran)；锗螺胺；替奴佐酸；三亚胺醌；2,2',2”-三氯三乙胺；单端孢霉烯类(尤其是T-2毒素、疣孢菌素(verracurin)A、杆孢菌素A和蛇行菌素)；乌拉坦(urethan)；长春地辛；达卡巴嗪；甘露莫司汀；二溴甘露醇；二溴卫矛醇；哌泊溴烷；gacytosine；阿糖胞苷(“Ara-C”)；环磷酰胺；塞替派；紫杉烷类，例如，
紫杉醇(Bristol-Myers Squibb Oncology,Princeton,N.J.)、
紫杉醇的不含克列莫佛的白蛋白工程改造的纳米颗粒制剂(American Pharmaceutical Partners,Schaumberg、Ill.)和
多西他赛(Rhone-Poulenc Rorer,Antony,法国)；瘤可宁(Chloranbucil)；
吉西他滨；6-硫鸟嘌呤；巯嘌呤；甲氨蝶呤；铂类似物诸如顺铂、奥沙利铂和卡铂；长春碱；铂；依托泊苷(VP-16)；异环磷酰胺；米托蒽醌；长春新碱；诺维本；长春瑞滨；诺肖林；替尼泊苷；依达曲沙；道诺霉素；氨基蝶呤；希罗达；伊班膦酸盐；伊立替康(Camptosar,CPT-11)(包括伊立替康与5-FU和亚叶酸的治疗方案)；拓扑异构酶抑制剂RFS2000；二氟甲基鸟氨酸(DMFO)；维A酸类诸如视黄酸；卡培他滨；考布他汀；亚叶酸(LV)；奥沙利铂，包括奥沙利铂治疗方案(FOLFOX)；拉帕替尼(Tykerb)；减少细胞增殖的PKC-α、Raf、H-Ras、EGFR(例如，厄洛替尼
)和VEGF-A的抑制剂和上述任一种的药学上可接受的盐、酸或衍生物或它们的组合。
“嵌合抗原受体”(CAR)是人工T细胞受体，其被设想用作癌症的靶向疗法，其使用称为过继性细胞转移的技术。受体多肽的基本抗原结合、信号传导和刺激功能已经通过基因重组方法简化至单个多肽链，其通常被称作嵌合抗原受体(CAR)(参见，例如，Eshhar,美国专利号7,741,465；Eshhar,美国专利申请公开号2012/0093842)。专门构建CAR以响应于CAR所结合的特定抗原刺激T细胞活化和增殖。术语“嵌合抗原受体”或可替换地“CAR”表示一组多肽，在最简单的实施方案中通常是两个，当在免疫效应细胞中表达时，它们为细胞提供对靶细胞(通常是癌细胞)的特异性，并提供细胞内信号产生。在一些实施方案中，CAR至少包含细胞外抗原结合结构域、跨膜结构域(参见，例如，SEQ ID NO:1)和细胞质信号传导结构域(在本文中也被称作“细胞内信号传导结构域”)，所述细胞质信号传导结构域包含从刺激性分子和/或共刺激分子衍生出的功能性信号传导结构域(参见，例如，SEQ ID NO:5)。在一些方面，该组多肽彼此邻接。在一个方面，刺激性分子是与T细胞受体复合物缔合的ζ链。在一个方面，细胞质信号传导结构域进一步包含从至少一种如下定义的共刺激分子衍生出的一个或多个功能性信号传导结构域。在一个方面，共刺激分子选自本文描述的共刺激分子，例如，4-lBB(即，CD137；SEQ ID NO:5)、CD27和/或CD28。在一个方面，CAR包含在CAR融合多肽的氨基-端(N-端)的任选前导序列(参见，例如，SEQ ID NO:6)。在一个方面，CAR进一步包含在细胞外抗原结合结构域的N-端的前导序列，其中所述前导序列任选地在CAR的细胞加工和向细胞膜的定位过程中从抗原结合结构域(例如，scFv)切割下来。通常使用“CAR-T细胞”，其表示已经工程改造成含有嵌合抗原受体的T-细胞。因而，带有这样的CAR的T淋巴细胞通常被称作CAR-T淋巴细胞。
“密码子优化”或“控制物种密码子偏爱”表示特定宿主细胞的优选密码子使用。如本领域技术人员会理解的，修饰编码序列以增强其在特定宿主中的表达可以是有利的。具有64种可能密码子的遗传密码是冗余的，但大多数生物体通常使用这些密码子的一部分。在物种中最常使用的密码子被称为最佳密码子，而那些不被经常使用的密码子被分类为稀有或利用率低的密码子。
可以制备含有被特定原核或真核宿主偏爱的密码子的优化编码序列(也参见,Murray等人(1989)Nucl.Acids Res.17:477-508)，例如，与由非优化序列产生的转录物相比，提高翻译速率或产生具有期望特性(诸如更长的半衰期)的重组RNA转录物。翻译终止密码子也可以被修饰以反映宿主偏好。本领域技术人员会认识到，由于遗传密码的简并性质，多种在它们的核苷酸序列中存在差异的DNA化合物可以用于编码本公开内容的给定多肽。
“保守置换”或“保守序列修饰”表示不显著影响或改变所编码的蛋白的结合特征或功能的氨基酸修饰。例如，“保守序列修饰”表示不显著影响或改变TCR恒定链、抗体、抗体片段或非免疫球蛋白结合结构域的结合特征或功能的氨基酸修饰。这样的保守修饰包括氨基酸置换、添加和缺失。通过本领域已知的标准技术，诸如定位诱变和PCR介导的诱变，可以将修饰引入TCR恒定链、抗体或抗体片段、非免疫球蛋白结合结构域或本公开内容的其它蛋白或多肽。保守氨基酸置换是其中氨基酸残基被具有类似侧链的氨基酸残基替换的氨基酸置换。具有类似侧链的氨基酸残基家族已经在本领域中定义。这些家族包括具有碱性侧链(例如，赖氨酸、精氨酸、组氨酸)、酸性侧链(例如，天冬氨酸、谷氨酸)、不带电荷的极性侧链(例如，甘氨酸、天冬酰胺、谷氨酰胺、丝氨酸、苏氨酸、酪氨酸、半胱氨酸、色氨酸)、非极性侧链(例如，丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸)、β-支链侧链(例如，苏氨酸、缬氨酸、异亮氨酸)和芳族侧链(例如，酪氨酸、苯丙氨酸、色氨酸、组氨酸)的氨基酸。因而，在本公开内容的SIR内的一个或多个氨基酸残基可以被来自相同侧链家族的其它氨基酸残基替代，并且可以使用本文所述的结合和/或功能测定测试改变的SIR。
如本文所使用的术语“源自”指示第一分子与第二分子之间的关系。它通常表示第一分子和第二分子之间的结构相似性，且不暗示或包括对源自第二分子的第一分子的过程或来源的限制。例如，在源自抗体分子的抗原结合结构域的情况下，抗原结合结构域保留了足够的抗体结构，使得它具有所需的功能，即结合抗原的能力。这不意味或不包括对产生抗体的特定过程的限制，例如，这不意味着为了提供抗原结合结构域，必须以抗体序列开始并删除不希望的序列或施加突变以达到抗原结合结构域。
作为本文中使用的术语，“细胞内信号传导结构域”表示分子的细胞内信号传导部分。细胞内信号传导结构域产生促进免疫细胞的免疫效应子功能的信号。免疫效应子功能的实例包括细胞裂解活性和辅助活性，包括细胞因子的分泌。
在另一个实施方案中，所述细胞内信号传导结构域可以包含初级细胞内信号传导结构域。示例性的初级细胞内信号传导结构域包括衍生自负责初级刺激或抗原依赖性模拟的分子的那些。在另一个实施方案中，所述细胞内信号传导结构域可以包含共刺激性细胞内结构域。示例性的共刺激性细胞内信号传导结构域包括衍生自负责共刺激信号或抗原非依赖性刺激的分子的那些。例如，初级细胞内信号传导结构域可以包含CD3z的细胞质序列，并且共刺激性细胞内信号传导结构域可以包含来自共受体或共刺激性分子(诸如CD28或41BB)的细胞质序列。
初级细胞内信号传导结构域可以包含信号传导基序，其被称作基于免疫受体酪氨酸的活化基序或ITAM。含有初级细胞质信号传导序列的ITAM的实例包括、但不限于衍生自CD3ζ、普通FeRγ(FCER1G)、FeγRIIa、FeRβ(Fe Epsilon R1b)、CD3γ、CD3δ、CD3ε、CD79a、CD79b、DAPlO和DAP12的那些。
本文中使用的术语“柔性多肽接头”表示由单独或组合使用的氨基酸(诸如甘氨酸和/或丝氨酸残基)组成的肽接头，以将多肽链连接在一起(例如，将可变重链和可变轻链区域连接在一起)。在一个实施方案中，所述柔性多肽接头是Gly/Ser接头且包含氨基酸序列(Gly-Gly-Gly-Ser)n，其中n是等于或大于1的正整数。例如，n＝l，n＝2，n＝3，n＝4，n＝5和n＝6，n＝7，n＝8，n＝9和n＝l0。在一个实施方案中，所述柔性多肽接头包括、但不限于(Gly4Ser)4或(Gly4Ser)3。在另一个实施方案中，所述接头包括(Gly2Ser)、(GlySer)或(Gly3Ser)的多个重复。
本文中使用的“哺乳动物”表示哺乳动物纲(Mammalia)的任何成员，包括、但不限于人类和非人灵长类动物诸如黑猩猩和其它猿和猴物种；农场动物诸如牛、绵羊、猪、山羊和马；家养哺乳动物诸如狗和猫；实验动物，包括啮齿类动物诸如小鼠、大鼠和豚鼠等。该术语不表示特定年龄或性别。因此，意图将成年和新生受试者以及胎儿(无论雄性还是雌性)包括在该术语的范围内。
术语“可操作地连接”表示第一组分和第二组分之间的功能性连接或关联，使得每个组分可以是功能性的。例如，可操作地连接包括调节序列和异源核酸序列之间的关联，从而导致后者的表达。例如，当将第一个核酸序列置于与第二个核酸序列的功能关联中时，所述第一个核酸序列与所述第二个核酸序列可操作地连接。在可操作地连接的两个多肽的上下文中，第一多肽以独立于任何连接的方式发挥功能，且第二多肽如同在两者之间不存在连接而发挥功能。
在两个或更多个核酸或多肽序列的上下文中，“同一性百分比”表示相同的两个或更多个序列。当在对比窗或指定区域中针对最大对应对比和比对(如使用下述序列对比算法之一或通过手工比对和目检所测量的)时，如果两个序列具有指定百分比的相同的氨基酸残基或核苷酸(例如，在指定区域上，或当未指定时，在整个序列上，60％同一性，任选地70％、71％、72％、73％、74％、75％、76％、77％、78％、79％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％同一性)，则所述两个序列是“基本上相同的”。任选地，同一性存在于至少约50个核苷酸(或10个氨基酸)长度的区域上，或更优选地存在于100至500或1000或更多个核苷酸(或20、50、200或更多个氨基酸)长度的区域上。
为了进行序列对比，通常一个序列充当参照序列，将测试序列与其对比。当使用序列对比算法时，将测试序列和参照序列输入计算机，如果必要的话，指定子序列坐标，并指定序列算法程序参数。可以使用默认程序参数，或可以指定替代参数。序列对比算法然后基于程序参数计算测试序列相对于参照序列的序列同一性百分比。用于对比的序列比对方法是本领域众所周知的。用于对比的序列的最佳比对可以例如通过下述方法进行：Smith和Waterman,(1970)Adv.Appl.Math.2:482c的局部同源性算法，Needleman和Wunsch,(1970)J.Mol.Biol.48:443的同源性比对算法，Pearson和Lipman,(1988)Proc.Nat'l.Acad.Sci.USA 85:2444的检索相似性方法，这些算法的计算机化实现(在威斯康辛州遗传学软件包中的GAP、BESTFIT、FASTA和TFASTA,Genetics Computer Group,575ScienceDr.,Madison,WI)，或手工比对和目检(参见，例如，Brent等人,(2003)Current Protocolsin Molecular Biology)。
可以用于确定序列同一性百分比和序列相似性的算法的两个实例是BLAST和BLAST 2.0算法，它们分别描述在Altschul等人,(1977)Nuc.Acids Res.25:3389-3402；和Altschul等人,(1990)J.Mol.Bioi.215:403-410。用于执行BLAST分析的软件可通过国家生物技术信息中心公开获得。
使用E.Meyers和W.Miller,(1988)Comput.Appl.Biosci.4:11-17的算法(该算法已经整合进ALIGN程序(2.0版)中)，使用PAM120加权残基表、12的缺口长度罚分和4的缺口罚分，也可以确定两个氨基酸序列之间的同一性百分比。另外，使用Needleman和Wunsch(1970)J.Mol.Bioi.48:444-453)算法(该算法已经整合进GCG软件包(可得自www.gcg.com)中的GAP程序中)，使用Blossom 62矩阵或P AM250矩阵，和16、14、12、10、8、6或4的缺口权重和1、2、3、4、5或6的长度权重，可以确定两个氨基酸序列之间的同一性百分比。
术语“多核苷酸”、“核酸”或“重组核酸”表示核苷酸诸如脱氧核糖核酸(DNA)和在适当的情况下核糖核酸(RNA)的聚合物。本领域技术人员会认识到，本文提供的任何DNA序列可以通过用‘U’替换‘T’而转化成RNA序列。
在本文中可互换地使用的术语“蛋白”或“多肽”包含一条或多条称为氨基酸的化学结构单元的链，所述氨基酸通过称为肽键的化学键连接在一起。
术语“RNV”表示非复制病毒载体，且可以是包含长末端重复序列、包装信号和克隆位点的逆转录病毒载体(参见，SEQ ID NO:12，其包含本公开内容的构建体的RNA主链序列)。从转化进生产/包装细胞系诸如HT1080衍生的包装细胞系HA-LB(Sheridan等人,Mol.Ther.,2:262-275,2000)或类似地构建的HA-L2包装细胞系中的包含SEQ ID NO:3的质粒，或通过将编码病毒蛋白的适当辅助基因组转染进其它有效生产细胞系的293T中，生产本公开内容的RNV。例如，通过用包含包装信号的SEQ ID NO:3的质粒转染包含gag、pol和env编码序列的包装细胞系，可以生产RNV。所述方法产生RNV，其中通过使用包装细胞，逆转录病毒基因组被包装在衣壳和包膜中。给包装细胞提供病毒蛋白-编码序列，通常以整合到细胞基因组中的两个质粒的形式，它们产生活的逆转录病毒颗粒的产生所必需的所有蛋白、编码RNA(其将携带所需基因)的DNA病毒构建体、以及包装信号(其将指导RNA包装到逆转录病毒颗粒中)。
术语“RNVCAR”表示非复制病毒载体，其包含长末端重复序列、包装信号且含有嵌合抗原受体(CAR)的编码序列。CAR包含靶向和选择性地结合任何数目的抗原(例如，癌症抗原等)的结合结构域。在一些情况下，本公开内容使用“X”-RNVCAR，其中X是特定抗原(例如，CD19-RNVCAR)的名称或首字母简略词。所述抗原可以被任何数目的如本文中所述的不同结合结构域(例如，scFv)靶向。可用于制备CAR构建体的各种结合结构域的序列是已知的(参见，例如，国际申请公开WO 2018/102795的表5；其序列和公开内容通过引用并入本文)。
术语“RRV”表示复制病毒载体，并且可以是包含长末端重复序列、gag、pol、env、包装信号和克隆位点的逆转录病毒载体。本公开内容的RRV不需要辅助细胞来产生感染性病毒粒子。在一些实施方案中，所述RRV包含：γ逆转录病毒GAG蛋白；γ逆转录病毒POL蛋白；γ逆转录病毒包膜；γ逆转录病毒RNA多核苷酸，其包含在γ逆转录病毒多核苷酸序列的3'末端处的来自鼠白血病病毒(MLV)、莫洛尼鼠白血病病毒(MoMLV)、猫白血病病毒(FeLV)、狒狒内源性逆转录病毒(BEV)、猪内源性病毒(PERV)、猫衍生的逆转录病毒RD114、松鼠猴逆转录病毒、嗜异性鼠白血病病毒相关病毒(XMRV)、禽网状内皮组织增殖病病毒(REV)或长臂猿白血病病毒(GALV)的3'非翻译区(U3)和重复区域(R)序列，在γ逆转录病毒多核苷酸的5'末端处的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的R和5'非翻译区(U5)序列，位于U5和U3区域之间的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的gag核酸结构域、pol核酸结构域和env核酸结构域；包含内部核糖体进入位点(IRES)、小启动子或2A或2A-样序列的盒，其在编码CAR编码序列的异源多核苷酸的上游并与其可操作地连接，其中所述盒位于U3区域的5'侧和env核酸结构域的3'侧；以及在靶细胞中的逆转录、包装和整合所必需的顺式作用序列。
术语“RRVCAR”表示复制病毒载体，其包含，例如，γ逆转录病毒GAG蛋白；γ逆转录病毒POL蛋白；γ逆转录病毒包膜；γ逆转录病毒RNA多核苷酸，其包含在γ逆转录病毒多核苷酸序列的3'末端处的来自鼠白血病病毒(MLV)、莫洛尼鼠白血病病毒(MoMLV)、猫白血病病毒(FeLV)、狒狒内源性逆转录病毒(BEV)、猪内源性病毒(PERV)、猫衍生的逆转录病毒RD114、松鼠猴逆转录病毒、嗜异性鼠白血病病毒相关病毒(XMRV)、禽网状内皮组织增殖病病毒(REV)或长臂猿白血病病毒(GALV)的3'非翻译区(U3)和重复区域(R)序列，在γ逆转录病毒多核苷酸的5'末端处的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的R和5'非翻译区(U5)序列，位于U5和U3区域之间的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的gag核酸结构域、pol核酸结构域和env核酸结构域；包含内部核糖体进入位点(IRES)、小启动子或2A或2A-样序列的盒，其在编码CAR编码序列的异源多核苷酸的上游并与其可操作地连接，其中所述盒位于U3区域的5'侧和env核酸结构域的3'侧；以及在靶细胞中的逆转录、包装和整合所必需的顺式作用序列。CAR包含靶向和选择性地结合任何数目的抗原(例如，癌症抗原等)的结合结构域。在一些情况下，本公开内容使用“X”-RRVCAR，其中X是特定抗原(例如，CD19-RRVCAR)的名称或首字母简略词。所述抗原可以被任何数目的如本文中所述的不同结合结构域(例如，scFv)靶向。可用于制备CAR构建体的各种结合结构域的序列是已知的(参见，例如，国际申请公开WO2018/102795的表5；其序列和公开内容通过引用并入本文)。
术语“scFv”表示融合蛋白，其包含至少一个含有轻链可变区的抗体片段和至少一个含有重链可变区的抗体片段，其中所述轻链和重链可变区是连续连接的，例如经由合成的接头，例如短的柔性多肽接头，并且能够被表达为单链多肽，并且其中scFv保留了衍生出它的完整抗体的特异性。除非另有说明，否则scFv可以具有任一种顺序的vL和vH可变区，例如，相对于多肽的N-端和C-端末端，scFv可以包含vL-(接头)-vH或可以包含vH-(接头)-vL。在本公开内容中，scFv也被描述为vL-(Gly-Ser-接头)-vH。
术语“信号传导结构域”表示蛋白的功能区，其如下通过限定的信号传导途径在细胞内传递信息以调节细胞活性：产生第二信使，或通过响应这样的信使而作为效应子发挥功能。
术语”受试者”意图包括在其中可以引起免疫应答的活生物体(例如，任何驯化的哺乳动物或人)。
术语“T-细胞”和“T-淋巴细胞”是可互换的，并且在本文中同义地使用。实例包括、但不限于原初T细胞(“淋巴细胞祖细胞”)、中央记忆T细胞、效应记忆T细胞、干记忆T细胞(Tscm)、iPSC-衍生的T细胞、合成的T细胞或它们的组合。
本文中使用的“治疗”和“处理”表示治疗性处理和预防性或防止性措施，其中目的是预防或减慢(减轻)目标病理状况，预防病理状况，追求或获得有益的结果，或降低个体发生病况的机会，即使治疗最终不成功。需要治疗的那些包括已经具有病况的那些以及易于具有病况的那些或要在其中预防病况的那些。
本文中使用的“肿瘤”表示所有赘生性细胞生长和增殖，无论恶性的还是良性的，和所有癌前的和癌性的细胞和组织。
本公开内容提供了在体内和离体产生CAR-T细胞的方法和组合物。所述组合物包括含有嵌合抗原受体(CAR)编码序列的重组载体(例如，病毒载体)，所述嵌合抗原受体(CAR)编码序列可以在体内整合到T-细胞或免疫细胞中。本公开内容的方法包括在体内引入(例如，通过静脉内施用)携带CAR编码序列的重组载体。
本公开内容提供了使用逆转录病毒非复制病毒(RNV)或复制感受态病毒(RRV)在体内将编码嵌合抗原受体(CAR)的载体静脉内递送至患者淋巴细胞(例如，T细胞)或其它免疫细胞，因此避免了目前采用的繁琐的离体转导策略。表达嵌合抗原受体(CAR)的T细胞被称为CAR T细胞——这涵盖合成的非-HLA限制的杂合分子，例如，来自单克隆抗体的外部靶抗原结合位点，以及修饰的或未修饰的HLA限制的常规T细胞受体亚基，该亚基识别细胞内HLA限制的表位呈递。含有嵌合抗原受体编码序列的RNV被称为RNVCAR。用表达CAR的RNVCAR转染的T细胞被称作γCAR-T细胞RNV。
本公开内容基于对多种因素的鉴定，包括：(a)从逆转录病毒载体生产系，任选地在无血清和/或悬浮培养物中，生产大量高滴度粗制RNVCAR；(b)纯化和浓缩载体以消除抗原蛋白污染物，使得可以将载体作为药物制品安全地静脉内施用给患者；(c)观察到，载体的小部分被患者T细胞吸收，并且这随着时间缓慢衰减；(d)认识到，识别靶标的特异性CART细胞随后将在体内扩增以达到治疗益处；(e)因为γ逆转录病毒仅有效感染复制中的细胞，所以静脉内施用导致活化的T细胞的转导，因为这些将是在血液中可访问的复制细胞的大百分比。相同的逻辑允许特异性刺激的/动员的细胞(诸如用粒细胞集落刺激因子(GCSF)动员的CD34造血干细胞)的靶向转导(A.Publicover等人,Brit.J.Haematology,162:107-111,2013)。通过施用各种临床上可接受的T细胞刺激策略，可以进一步激发循环中的T细胞群体用于体内载体摄取，所述策略包括、但不限于：接种活的或减毒的病毒疫苗，诸如麻疹、牛痘或一些流感疫苗；细胞因子刺激(IL2等)；施用变态反应小组测试，临床上可接受的人类剂量中的各种超抗原，单克隆抗体诸如OKT3(莫罗单抗-CD3)。
还可将RNVCAR工程改造为“安全修饰的”，以减少在一些靶细胞群体中插入基因活化的可能性(Schambach等人,Methods in Molecular Biology,Methods and Protocols,506:191-205,2009)，例如具有自失活(SIN)构型。各种“SIN”构型是本领域已知的。
“自失活”(SIN)载体表示复制缺陷型载体，例如逆转录病毒或慢病毒载体，其中被称为U3区域的3'LTR增强子-启动子区域已经被修饰(例如，通过缺失或置换)，以防止超出第一轮病毒复制的病毒转录。这是因为，在病毒复制期间，LTR U3区域被用作5'LTR U3区域的模板，且因此，在没有U3增强子-启动子的情况下不可产生病毒转录物。在另一个实施方案中，修饰3'LTR，使得U5区域被例如理想的聚腺苷酸序列替换。应当指出，对LTR的修饰，例如对3'LTR、5'LTR、或3'和5'LTR两者的修饰，也被包括在本公开内容中。
通过用异源启动子替代5'LTR的U3区域以在病毒颗粒产生期间驱动病毒基因组的转录，可以提供额外的安全性增强。可以使用的异源启动子的实例包括、例如：病毒猿猴病毒40(SV40)(例如，早期或晚期)，巨细胞病毒(CMV)(例如，立即早期)，莫洛尼鼠白血病病毒(MoMLV)，劳斯肉瘤病毒(RSV)，和单纯疱疹病毒(HSV)(胸苷激酶)启动子。典型的启动子能够以不依赖Tat的方式驱动高水平的转录。这种替换降低了重组产生具有复制能力的病毒的可能性，因为在病毒生产系统中没有完整的U3序列。在某些实施方案中，异源启动子在控制转录病毒基因组的方式方面具有额外优点。例如，异源启动子可以是可诱导的，使得全部或部分病毒基因组的转录仅在存在诱导因子时才发生。诱导因子包括、但不限于一种或多种化学化合物或在其中培养宿主细胞的生理条件，诸如温度或pH。
经工程改造的RNVCAR还可以含有“控制”基因，诸如前药活化基因，包括、但不限于疱疹胸苷激酶、嘌呤核苷磷酸化酶、胞嘧啶脱氨酶或硝基还原酶，或可二聚化的死亡或细胞凋亡诱导蛋白，诸如具有突变的FK506可二聚化尾巴的Cas9杂合物，以在达到治疗终点后或当发生临床上重要的副作用(诸如自身抗原或脱靶相关的不利事件或肿瘤细胞的非故意转导，所述非故意转导可能使肿瘤不可被CAR T-细胞识别)时删除CAR T细胞。
经工程改造的RNVCAR还可以含有“活化增强”RNA表达修饰剂，诸如非编码RNA或蛋白诸如单链抗体，affimers，其特异性下调T细胞检查点抑制剂诸如PD-1、CTLA-4或其它适当免疫辅助分子的激动剂的表达。在这样的实施方案中，RNV将转导患者T细胞，使得CAR T细胞表达嵌合抗原受体、“控制”基因诸如胞嘧啶脱氨酶、以及降解PD-1转录物并随后降低PD-1蛋白水平的shRNA。
本公开内容允许通过使用携带针对多种抗原和表位的嵌合受体的RNVCAR的混合物同时静脉内递送针对多种肿瘤相关抗原和肿瘤新抗原或其它疾病相关抗原的多种嵌合受体。
嵌合抗原受体向T细胞的RNVCAR递送不是适应症特异性治疗的，并且可以与个性化的癌症或疾病概况分析相组合，以选择最可能结合被患者表达的抗原和新抗原的嵌合受体，而与适应症无关。单独的RNVCAR的静脉内递送具有不同抗原结合能力的嵌合受体的能力允许临时治疗方案，该方案可以允许新CAR在选择性压力和肿瘤或疾病适应后被递送，从而删除原始CAR表位。RNVCAR可以与免疫治疗增强剂诸如检查点抑制剂(例如抗-CTLA4和抗-PD-1)、抗肿瘤逃逸靶向药物(例如IDO-1抑制剂和抗-TGFβ)和/或具有已知免疫调节作用的化疗剂(例如，替莫唑胺,环磷酰胺和5-FU)联合使用。
通过在RNVCAR静脉内注射时使用T细胞活化佐剂(例如，3-O-去酰基-4'-单磷酰脂质A(MPL)和干扰素γ)，可以增强嵌合受体向患者T细胞的RNV递送。RNV可能通过淋巴递送，并在适当的情况下递送到实体瘤适应症的引流淋巴结，预期在此处呈递肿瘤相关的抗原和新抗原。
RNV也可以被假型化以增加T细胞的转导效率(例如GALV、双嗜性的env或麻疹病毒糖蛋白H和F)或指导T细胞亚型的特异性(例如，使用嵌合C-HIV包膜假型的记忆CD4 T细胞或带有MLV-10A1包膜的CD8 T细胞)。
使用逆转录病毒非复制病毒(RNV)将嵌合抗原受体直接递送至患者T细胞，避免了目前采用的繁琐的离体转导策略(参见表3)。
表3:用逆转录病毒载体体内和离体转导自体细胞的步骤的对比
在一个实施方案中，将包含用于靶向感兴趣的抗原/同源物(例如，CD19)的编码结构域的RNVCAR作为药学上可接受的制剂在体内递送至人患者T细胞。例如，将CD19-RNVCAR静脉内注射到血流中以递送至人T细胞。这种静脉内递送可以作为快速推注或通过在数分钟至数小时内的缓慢输注进行。可以在数天中重复注射，以增加获得转导的T细胞的频率和可能性。通过施用各种T细胞刺激策略，可以进一步引发T细胞群体用于体内RNVCAR载体摄取：接种活病毒疫苗(诸如麻疹、牛痘或一些流感疫苗)；加入目前已批准用在人类疫苗中的佐剂赋形剂，刺激T细胞的细菌蛋白(直接和间接)，细胞因子刺激(IL2等)，变态反应小组测试的施用，临床可接受的人类剂量中的各种超抗原，单克隆抗体诸如OKT3(莫罗单抗-CD3)，和使用药物诸如环磷酰胺的骨髓消耗。通过在RNVCAR静脉内注射时使用T细胞活化佐剂(例如3-O-去酰基-4'-单磷酰脂质A(MPL)和干扰素γ)，可以增强向患者T细胞的RNVCAR递送。这些RNVCAR可以与免疫治疗增强剂诸如检查点抑制剂(例如抗-CTLA4和抗-PD-1)、抗肿瘤逃逸靶向药物(例如IDO-1抑制剂和抗-TGFβ)、具有已知免疫调节作用的化疗剂(例如，替莫唑胺和5-FU)或个性化的新抗原疫苗联合使用。
RNV也可以被假型化以增加T细胞的转导效率(例如，GALV、双嗜性的env或麻疹病毒糖蛋白H和F)或指导T细胞亚型的特异性(例如，使用嵌合C-HIV包膜假型的记忆CD4 T细胞或带有MLV-10A1包膜的CD8 T细胞)。使用这些静脉内方法对RNVCAR(例如，CD19-RNVCAR)的递送产生靶向和破坏细胞、微生物等的患者T细胞，所述细胞、微生物等表达被RNVCAR的结合结构域特异性地识别的抗原(例如，在CD19-RNVCAR转导的T-细胞将靶向并破坏CD19+细胞的情况下)。
在另一个实施方案中，将RNVCAR通过淋巴递送，并且在适当的时候递送至实体瘤适应症的引流淋巴结，预期在那里呈递肿瘤相关的抗原和新抗原。通过如上所述使用佐剂和组合类似地增强了淋巴结的直接注射。
在向人T细胞的RNVCAR(例如，CD19-RNVCAR)递送的另一个实施方案中，所述方法包括向RNVCAR添加单纯疱疹病毒-胸苷激酶(HSV-TK)、酵母胞嘧啶脱氨酶(CD)或其它自杀基因或前药活化剂系统，作为在不利事件的情况下或治疗结束时消耗转导的细胞的方法。例如，将编码CD19-CAR的RNVCAR载体用TK、CD或其它“控制”基因工程改造(例如，Tocagen的修饰的酵母胞嘧啶脱氨酶；参见，美国专利号8,722,867，其公开内容通过引用并入本文)。通过与上述相同的方法/过程来递送该修饰的RNVCAR。使用放射性地标记的嘧啶(胸苷)和嘌呤(无环鸟苷)衍生物作为用PET对HSV-TK酶活性进行成像的报告探针，可以将RNVCAR(例如，CD19-RNVCAR)追踪到肿瘤。包括前药活化酶诸如HSV-TK或CD的另一个优点是，如果也用CAR载体转导了特定低百分比的肿瘤细胞并且此事件使转导的肿瘤细胞对T细胞中的CAR无应答(M.Ruella等人.Nat.Med.,24:1499-1503,2018)，这样的肿瘤细胞将分别被一系列前药(例如伐昔洛韦或5-氟胞嘧啶)自动消除。
本公开内容提供了重组核酸构建体，其包含编码靶向本文所鉴定的任何抗原的CAR的核酸分子。在一个实施方案中，所述核酸序列包含DNA质粒构建体，所述DNA质粒构建体包含已将CAR构建体克隆入其中的SEQ ID NO:3。例如，SEQ ID NO:18至22提供了衍生自SEQ ID NO:3且包含靶向CD19的各种CAR构建体的质粒序列。
在另一个实施方案中，本公开内容提供了一种RNVCAR，其包含包装到病毒衣壳中的RNA序列。通过如下获得RNVCAR：将含有CAR并且包含SEQ ID NO:3的核酸构建体转染到包装细胞系中，并培养该细胞系以产生RNVCAR。RNVCAR将包含SEQ ID NO:12并包含编码所需CAR构建体(例如，靶向至所需抗原的CAR构建体)的RNA序列。
本公开内容还提供了包含一种或多种核酸序列的一种或多种载体，所述核酸序列编码本文描述的RNV、RNVCAR或包含自杀/前药活化剂序列的RNV。在一个实施方案中，本公开内容提供了由单个载体编码的一种RNVCAR构建体。在另一个实施方案中，本公开内容提供了超过一种载体，例如，一种编码CAR的载体和第二种编码自杀/前药活化剂基因的载体。在一个实施方案中，一种或多种载体选自DNA载体、RNA载体、质粒、γ-逆转录病毒载体。在一个实施方案中，所述载体是包含LTR和包装序列的肠内(gutted)-γ逆转录病毒载体。
可以使用任何多种不同方法中的任何一种将DNA和/或RNA导入靶细胞，所述方法例如，商购可得的方法，包括、但不限于电穿孔(Amaxa Nucleofector-II(AmaxaBiosystems,Cologne,德国)),(ECM 830(BTX)(Harvard Instruments,Boston,Mass.)或Gene Pulser II(BioRad,Denver,Colo.),Multiporator(Eppendort,Hamburg德国)，阳离子脂质体介导的使用脂转染的转染，聚合物包封，肽介导的转染，或生物弹道颗粒递送系统诸如“基因枪”(参见，例如，Nishikawa,等人.Hum Gene Ther.,12(8):861-70(2001)或通过使用微流控装置造成在细胞膜中的短暂干扰(参见，例如，专利申请WO 2013/059343 A1和PCT/US2012/060646)。
在另一个实施方案中，提供了一种治疗受试者的方法，例如，减轻或改善受试者中的过度增殖病症或病况(例如，癌症，包括、但不限于实体瘤、软组织肿瘤、血癌或转移性病变)的方法。本文中使用的术语“癌症”意在包括所有类型的癌性生长或致癌过程、转移性组织或恶性转化的细胞、组织或器官，而与组织病理学类型或侵入性阶段无关。示例性的实体瘤包括各种器官系统的恶性肿瘤，例如，腺癌、肉瘤和癌，诸如影响乳房、肝、肺、脑、淋巴、胃肠(例如，结肠)、生殖泌尿道(例如，肾、泌尿道上皮细胞)、前列腺和咽的那些。腺癌包括癌症诸如大多数结肠癌、直肠癌、肾细胞癌、肝癌、非小细胞肺癌、小肠癌和食管癌。在一个实施方案中，所述癌症是黑素瘤，例如，晚期黑素瘤。还可以使用本公开内容的方法和组合物治疗或预防上述癌症的转移性病变。可以治疗或预防的其它癌症的实例包括胰腺癌、骨癌、皮肤癌、皮肤或眼内恶性黑素瘤、子宫癌、卵巢癌、直肠癌、头或颈癌、肛门区域的癌症、胃癌、睾丸癌、子宫癌、输卵管癌、子宫内膜癌、子宫颈癌、阴道癌、外阴癌、霍奇金病、非霍奇金淋巴瘤、食管癌、小肠癌、内分泌系统的癌症、甲状腺癌、甲状旁腺癌、肾上腺癌、软组织肉瘤、尿道癌、阴茎癌、慢性或急性白血病(包括急性髓性白血病、慢性髓性白血病、急性成淋巴细胞性白血病、慢性淋巴细胞白血病)、儿童期的实体瘤、淋巴细胞性淋巴瘤、膀胱癌、肾或输尿管的癌症、肾盂癌、中枢神经系统(CNS)的赘生物、原发性CNS淋巴瘤、肿瘤血管生成、脊髓轴肿瘤、脑干神经胶质瘤、垂体腺瘤、卡波西氏肉瘤、表皮样癌、鳞状细胞癌、T-细胞淋巴瘤、环境诱发的癌症(包括由石棉诱发的那些)、和所述癌症的组合。所述方法包括施用本公开内容的RNVCAR，其包含特异性地结合在癌细胞上存在的抗原的CAR。
其生长可被抑制的示例性癌症包括通常对免疫疗法有应答的癌症。用于治疗的癌症的非限制性实例包括肾癌(例如透明细胞癌)、黑素瘤(例如，转移性恶性黑素瘤)、乳腺癌、前列腺癌(例如激素难治的前列腺腺癌)、结肠癌和肺癌(例如非小细胞肺癌)。
提供以下实施例以进一步举例说明但不限制所公开的发明。本领域技术人员考虑到本公开内容会容易明白以下实施例的其它方法或变型。
实施例
用于通过非复制病毒体内递送的鼠CD19嵌合抗原受体构建体的设计.将非复制载体(RNV)构建成含有嵌合抗原受体(CAR)。在第一个实施例中，开发了RNVCAR并靶向针对鼠CD19。使用从大鼠杂交瘤克隆1D3构建的单链可变片段(scFv)实现鼠CD 19靶向。所述scFv含有1D3可变重链(VH)，随后是与1D3可变轻链(VL)的GS接头。靶向鼠的scFv的氨基酸序列在表4中列出。编码鼠CD19 scFv的核苷酸可以是被认为最适合于病毒载体表达和稳定性的任何密码子。编码1D3 scFv(VH-GS-VL)的核苷酸序列可以从以下之一表达：逆转录病毒载体启动子(例如，LTR)、内部启动子、内部核糖体进入位点(IRES)(参见，例如，WO2010036986,通过引用并入本文)、或在逆转录病毒载体中的蛋白融合策略(例如，使用弗林蛋白酶肽酶位点，或2A盒；参见，例如，美国专利公开号2018/0251786A1，其通过引用整体并入本文)。所述scFv在框架内后面是编码人CD8铰链结构域、鼠CD8铰链结构域或鼠CD28铰链结构域的核苷酸序列，如表5中所示。所述铰链结构域在框架内后面是编码人CD8跨膜结构域(TMD)、鼠CD8TMD或鼠CD28TMD的核苷酸序列，如表5中所示。所述跨膜结构域在框架内后面是编码人4-1BB细胞内信号传导结构域(ICD)、鼠4-1BB ICD或鼠CD28 ICD的核苷酸序列，如表5中所示。所述细胞内结构域在框架内后面是编码人CD3ζ细胞内信号传导结构域(ICD)或鼠CD3ζICD的核苷酸序列，如表5中所示。然后可以静脉内地(IV)或脾内地递送在RNV载体中的完整的靶向鼠CD19的CAR构建体，以实现在T细胞中的最佳CAR递送、转导和表达。
表4
表5
在小鼠中静脉内施用后RNV对免疫细胞的感染.为了评价通过静脉内施用的RNV的感染潜力，在Balb/c小鼠中评价了表达绿色荧光蛋白的RNV(RNV-GFP)。连续3天以每天1E7或1E8 TU(滴度单位)的剂量静脉内施用RNV，有或没有用100mg/kg环磷酰胺预处理。在RNV-GFP的第一个静脉内剂量后7天，在外周血单核细胞(PBMC)中确定了RNV-GFP感染(图6)。在3E7 TU的总剂量，所有CD45+PBMC的0.045％是GFP阳性的(GFP+)。经环磷酰胺预处理，GFP+、RNV感染的(GP+)CD45+细胞增加至0.137％。在3E8 TU的总剂量，CD45+PBMC的3.08％和2.02％(经环磷酰胺预处理)对于RNV-GFP的GFP感染是阳性的。
在PBMC群体的子集中评价了RNV-GFP感染：CD11b+、CD4+、CD8+和CD19+(图7)。在RNV-GFP的较低剂量、3E7 TU的总剂量，每个PBMC群体中的小于0.5％是GFP+。环磷酰胺预处理向剂量3E7 TU的添加通常导致每个群体中的GFP+细胞的倍增，约1％GFP+。在RNV-GFP的较高剂量、3E3 TU的总剂量，每个评价的PBMC群体的约10％是GFP+。环磷酰胺预处理向剂量3E8 TU的添加对每个评价的PBMC群体中的GFP+、RNV感染的细胞的百分比没有明显影响。
B细胞淋巴瘤的小鼠模型的治疗.将Balb/c小鼠中的A20淋巴瘤系(Kueberuwa等人,J.Vis.Exp.,(140),e58492,2018,doi:10.3791/58492 2018)用作模型以评价初始小鼠靶向构建体mCD19-RNVCAR(RNV-1D3CAR)的体内感染效力：小鼠抗-CD19 scFv 1D3，接着是鼠CD8跨膜结构域，接着是鼠4-1BB细胞内结构域，接着是鼠CD3ζ细胞内结构域。简而言之，在植入A20淋巴瘤细胞前1天，向6-8-周龄BALB/c小鼠腹膜内(IP)施用100mg/kg环磷酰胺。环磷酰胺预处理允许将A20肿瘤移植物植入淋巴结，而无明显的淋巴细胞耗竭。在第0天静脉内注射A20 B-细胞淋巴瘤细胞(在100μL中的5E5个细胞)。从A20植入后的第5天开始，连续5天每天以1E7或1E8 TU的剂量注射载体RNV-1D3CAR。监测小鼠37天并评估存活率。
与媒介物处理的对照组(无RNV)或较低剂量的RNV-1D3CAR相比，较高剂量的RNV-1D3CAR(5E8 TU)导致A20淋巴瘤荷瘤小鼠中的存活率改善(5E7,参见图8)。高剂量RNV-1D3CAR处理的小鼠的存活率改善提示，mCD19-RNVCAR载体的静脉内施用在一定程度上控制A20肿瘤生长。为了在RNV-1D3CAR的静脉内施用后发生肿瘤控制，载体必须进入循环T细胞，mCD19-CAR必须在那些T细胞的表面上表达，那些T细胞然后必须归巢至肿瘤(主要是淋巴结)，且最后，在T细胞表面上的mCD19-CAR必须与A20肿瘤细胞上的CD 19接合并活化A20肿瘤细胞的杀死。
pBA9b-hCD19CAR载体的构建.pBA9b(SEQ ID NO:3)提供了基于MLV的逆转录病毒非复制载体(RNV)，其含有延伸的包装区域。
对靶向人CD19的各种单链可变片段(scFv)的核酸序列、前导序列、源自人CD8的铰链结构域、源自人CD8的跨膜结构域、源自人4-1BB的细胞内结构域和源自人CD3ζ的信号传导结构域进行密码子优化和合成(Genewiz Inc.)。本公开内容提供了五种合成的hCD19CAR核酸序列，分别命名为：hCD19CAR1(SEQ ID NO:13)、hCD19CAR2(SEQ ID NO:14)、hCD19CAR3(SEQ ID NO:15)、hCD19CAR4(SEQ ID NO:16)、hCD19CAR5(SEQ ID NO:17)，并且分别含有在5’和3’处的Not I和Sal I限制性酶位点，用于在对应的限制性酶位点(“MCS”)处定向克隆入pBA9b主链(SEQ ID NO:3)。得到的质粒DNA被命名为pBA9b-hCD19CAR1、pBA9b-hCD19CAR2、pBA9b-hCD19CAR3、pBA9b-hCD19CAR4和pBA9b-hCD19CAR5(分别是SEQ ID NO:18、19、20、21和22)。在所有构建体中，CD19-CAR表达由病毒LTR启动子介导(图5A-B)。
非克隆HAL2-hCD19CAR载体生产细胞系(VPCL)产生高hCD19-RNVCAR病毒滴度.产生非克隆HAL2-hCD19CAR生产细胞以证实病毒产生，hCD19CAR表达。首先通过在293GP生产细胞中瞬时转染而产生用VSV-G假型化的pBA9b-hCD19CAR载体。随后，以100的感染复数(MOI)转导稳定表达基于MLV的gag-pol和4070A双嗜性衣壳蛋白的HAL2生产细胞。293GP细胞源自稳定生产基于MLV的gag-pol的HEK293细胞。HAL2是以与VPCL HA-LB相同的方式构建的人包装细胞系(Sheridan等人,Mol.Ther.2000)。使用qPCR方法(5-MLV-U3-B:5’-AGCCCACAACCCCTCACTC-3’(SEQ ID NO:120),3-MLV-Psi:5’-TCTCCCGATCCCGGACGA-3’(SEQID NO:121),探针:FAM-5’-CCCCAAATGAAAGACCCCCGCTGACG-3’-BHQ1(SEQ ID NO:122))在人前列腺PC-3细胞上滴定从稳定转导的细胞产生的所有pBA9b-hCD19CAR载体。结果显示，由HAL2细胞产生的pBA9b-hCD19CAR载体的滴度值范围为5E5-1E7 TU/mL。
为了证实hCD19CAR的表达，用FITC-缀合的重组人CD19蛋白(ACROBiosystems,CD9-HF2H2)染色2×105个hCD19CAR VPCL细胞。在流式细胞仪(Canto,BD Biosciences)上分析细胞以证实CD19与细胞表面上的hCD19CAR的结合，作为在VPCL细胞表面上的hCD19CAR表达的替代读数。另外，也通过抗-CD3ζ抗体(abcam,ab200591)通过免疫印迹法证实了hCD19CAR表达。
克隆HAL2-hCD19CAR载体生产细胞系(VPCL)产生高hCD19-RNVCAR病毒滴度用于制造.将来自非克隆VPCL的细胞接种到五个96-孔平板中，基于细胞计数和有限稀释，目标是每个孔1个细胞。使证实包含单个细胞的孔生长至75％汇合，用于使用MLV特异性引物和探针通过qRT-PCR筛选高滴度生产克隆。然后将选定的高滴度生产克隆转移到6孔板中，然后转移到T75烧瓶中进行细胞扩增和进一步表征，包括生长特征、逆转录病毒组分的稳定性、滴度、载体拷贝数和转基因表达。在T75烧瓶中选择和培养的前25个高滴度生产克隆中，它们在5天分析滴度测定中产生E6-2E8 TU/mL的病毒滴度范围。随后，从选择的最高滴度克隆中产生工作细胞库，并测试一组安全性评估，包括无菌性和支原体、细菌污染、不存在RCR和包括牛病毒在内的其它偶发因子。
除了所鉴定的安全性测试的清单之外，还测试了来自工作细胞库和主细胞库的小瓶以证实细胞形态学、生存力、载体序列的完整性、平均载体拷贝数、细胞倍增时间和通过转导滴度的载体产生。
如在Sheridan等人(在引用的作品中)和美国专利号10,316,333(通过引用并入本文)中所述，通过大规模细胞发酵生产hCD19-RNVCAR临床材料，并随后通过如下纯化(J.S.Powell等人,Blood,102:2038-2045,2003)：通过离子交换柱，然后在制剂缓冲液(蔗糖和磷酸盐或Tris缓冲盐水)中进行尺寸排阻色谱法，然后穿过0.2微米过滤器过滤到2-5ml管形瓶中。通常这导致5E7-1E9/ml TU/ml的纯化的配制载体制品。对于GMP材料，这在赞助商批准的GMP合同制造设施进行。
使用培养的人PBMC,通过方法诸如M.C.Milone等人,Molecular Therapy,17:1453-1464,2009和C.Sommer等人,Mol Ther.,27:1126-1138,2019描述的那些方法，在体外测试载体的效力，并在异种移植物小鼠模型中进一步测试，例如，Milone等人(出处同上)，其中使用输注的人PBMC，随后静脉内施用载体。
B细胞淋巴瘤患者的治疗.以1xE5、1xE6、1xE7、1xE8、1xE9和1xE10TU/kg的载体剂量，静脉内施用给具有CD19+复发性或难治性B-细胞急性成淋巴细胞性白血病(ALL)的年轻成年患者。在较高剂量组群中，在3个月内的总减轻率为大约75％，发现对治疗有应答的所有患者是最小残留疾病阴性的，如借助于流式细胞计量术评估的。无事件存活率和总存活率在6个月时分别大部分超过60％和90％，并且在12个月时则大部分超过35％和60％。确切的数字最初取决于患者的状况，但在离体测试中与年轻成年人相当，如Maude等人,N.Eng.J.Med.,378:439-449,2018所述。效用的总体标准是>20％的3个月缓解率。
已经描述了本公开内容的许多实施方案。尽管如此，应该理解，在不脱离本公开内容的精神和范围的情况下，可以做出各种修改。因此，其它实施方案在下述权利要求的范围内。
序列表
<110> 托卡根公司
<120> CAR T细胞方法和构建体
<130> 00014-036WO1
<140> 尚未指定
<141> 2020-01-06
<150> US 62/788,894
<151> 2019-01-06
<160> 122
<170> PatentIn 3.5版
<210> 1
<211> 72
<212> DNA
<213> 人工序列
<220>
<223> 人CD8跨膜结构域
<400> 1
atctacatct gggcgccctt ggccgggact tgtggggtcc ttctcctgtc actggttatc 60
accctttact gc 72
<210> 2
<211> 135
<212> DNA
<213> 人工序列
<220>
<223> 人CD8铰链/间隔物结构域
<400> 2
accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg 60
tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg 120
gacttcgcct gtgat 135
<210> 3
<211> 4832
<212> DNA
<213> 人工序列
<220>
<223> pBA9b质粒序列
<400> 3
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgctcgcg agtcgacaag cttggatcca tcgataaaat aaaagatttt atttagtctc 1980
cagaaaaagg ggggaatgaa agaccccacc tgtaggtttg gcaagctagc ttaagtaacg 2040
ccattttgca aggcatggaa aaatacataa ctgagaatag agaagttcag atcaaggtca 2100
ggaacagatg gaacagctga atatgggcca aacaggatat ctgtggtaag cagttcctgc 2160
cccggctcag ggccaagaac agatggaaca gctgaatatg ggccaaacag gatatctgtg 2220
gtaagcagtt cctgccccgg ctcagggcca agaacagatg gtccccagat gcggtccagc 2280
cctcagcagt ttctagagaa ccatcagatg tttccagggt gccccaagga cctgaaatga 2340
ccctgtgcct tatttgaact aaccaatcag ttcgcttctc gcttctgttc gcgcgcttct 2400
gctccccgag ctcaataaaa gagcccacaa cccctcactc ggcgcgccag tcctccgatt 2460
gactgagtcg cccgggtacc cgtgtatcca ataaaccctc ttgcagttgc atccgacttg 2520
tggtctcgct gttccttggg agggtctcct ctgagtgatt gactacccgt cagcgggggt 2580
ctttcatttg aagccgaatt cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 2640
tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 2700
ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 2760
aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 2820
tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 2880
gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 2940
cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 3000
gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 3060
aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 3120
ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 3180
cccttcggga agcgtggcgc tttctcaaag ctcacgctgt aggtatctca gttcggtgta 3240
ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 3300
cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 3360
agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 3420
gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 3480
gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 3540
tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 3600
agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 3660
agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 3720
atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 3780
cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 3840
actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 3900
aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 3960
cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 4020
ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 4080
cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 4140
ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 4200
cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 4260
ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 4320
tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 4380
ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 4440
aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 4500
gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 4560
gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 4620
ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 4680
catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 4740
atttccccga aaagtgccac ctgacgtcta agaaaccatt attatcatga cattaaccta 4800
taaaaatagg cgtatcacga ggccctttcg tc 4832
<210> 4
<211> 336
<212> DNA
<213> 人工序列
<220>
<223> 人CD3ζ细胞内结构域
<400> 4
agagtgaagt tcagcaggag cgcagacgcc cccgcgtaca agcagggcca gaaccagctc 60
tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc 120
cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat 180
gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc 240
cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc 300
tacgacgccc ttcacatgca ggccctgccc cctcgc 336
<210> 5
<211> 126
<212> DNA
<213> 人工序列
<220>
<223> 人4-1BB细胞内结构域
<400> 5
aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa 60
actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt 120
gaactg 126
<210> 6
<211> 63
<212> DNA
<213> 人工序列
<220>
<223> 前导序列
<400> 6
atggccctgc ctgtgacagc cctgctgctg cctctggctc tgctgctgca tgccgctaga 60
ccc 63
<210> 7
<211> 107
<212> PRT
<213> 人工序列
<220>
<223> 鼠CD19可变重链
<400> 7
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Thr Ser Leu Gly
1 5 10 15
Glu Thr Val Thr Ile Gln Cys Gln Ala Ser Glu Asp Ile Tyr Ser Gly
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Asp Leu Gln Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Thr Ser Met Gln Thr
65 70 75 80
Glu Asp Glu Gly Val Tyr Phe Cys Gln Gln Gly Leu Thr Tyr Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 8
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> GS接头
<400> 8
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 9
<211> 116
<212> PRT
<213> 人工序列
<220>
<223> 鼠CD19可变轻链
<400> 9
Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Val Ser Gly Asp Thr Ile Thr Phe Tyr
20 25 30
Tyr Met His Phe Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Glu Asp Glu Ser Thr Lys Tyr Ser Glu Lys Phe
50 55 60
Lys Asn Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr
65 70 75 80
Leu Lys Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys
85 90 95
Ile Tyr Gly Gly Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Val Met Val
100 105 110
Thr Val Ser Ser
115
<210> 10
<211> 138
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD8铰链/间隔物结构域
<400> 10
tctactacta ccaagccagt gctgcgaact ccctcacctg tgcaccctac cgggacatct 60
cagccccaga gaccagaaga ttgtcggccc cgtggctcag tgaaggggac cggattggac 120
ttcgcctgtg atatttac 138
<210> 11
<211> 108
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD28铰链/间隔物结构域
<400> 11
attgagttca tgtaccctcc gccttaccta gacaacgaga ggagcaatgg aactattatt 60
cacataaaag agaaacatct ttgtcatact cagtcatctc ctaagctg 108
<210> 12
<211> 1662
<212> RNA
<213> 人工序列
<220>
<223> pBA-9b vRNA基因组
<400> 12
gcgccagucc uccgauugac ugagucgccc ggguacccgu guauccaaua aacccucuug 60
caguugcauc cgacuugugg ucucgcuguu ccuugggagg gucuccucug agugauugac 120
uacccgucag cgggggucuu ucauuugggg gcucguccgg gaucgggaga ccccugccca 180
gggaccaccg acccaccacc gggagguaag cuggccagca acuuaucugu gucuguccga 240
uugucuagug ucuaugacug auuuuaugcg ccugcgucgg uacuaguuag cuaacuagcu 300
cuguaucugg cggacccgug guggaacuga cgaguucgga acacccggcc gcaacccugg 360
gagacguccc agggacuucg ggggccguuu uuguggcccg accugagucc aaaaaucccg 420
aucguuuugg acucuuuggu gcaccccccu uagaggaggg auaugugguu cugguaggag 480
acgagaaccu aaaacaguuc ccgccuccgu cugaauuuuu gcuuucgguu ugggaccgaa 540
gccgcgccgc gcgucuuguc ugcugcagca ucguucugug uugucucugu cugacugugu 600
uucuguauuu gucugagaau uaaggccaga cuguuaccac ucccugaagu uugaccuuag 660
gucacuggaa agaugucgag cggaucgcuc acaaccaguc gguagauguc aagaagagac 720
guuggguuac cuucugcucu gcagaauggc caaccuuuaa cgucggaugg ccgcgagacg 780
gcaccuuuaa ccgagaccuc aucacccagg uuaagaucaa ggucuuuuca ccuggcccgc 840
auggacaccc agaccagguc cccuacaucg ugaccuggga agccuuggcu uuugaccccc 900
cucccugggu caagcccuuu guacacccua agccuccgcc uccucuuccu ccauccgccc 960
cgucucuccc ccuugaaccu ccucguucga ccccgccucg auccucccuu uauccagccc 1020
ucacuccuuc ucuaggcgcc ggaauuaauu cucgaggggc ccagaucugc ggccgcucgc 1080
gagucgacaa gcuuggaucc aucgauaaaa uaaaagauuu uauuuagucu ccagaaaaag 1140
gggggaauga aagaccccac cuguagguuu ggcaagcuag cuuaaguaac gccauuuugc 1200
aaggcaugga aaaauacaua acugagaaua gagaaguuca gaucaagguc aggaacagau 1260
ggaacagcug aauaugggcc aaacaggaua ucugugguaa gcaguuccug ccccggcuca 1320
gggccaagaa cagauggaac agcugaauau gggccaaaca ggauaucugu gguaagcagu 1380
uccugccccg gcucagggcc aagaacagau gguccccaga ugcgguccag cccucagcag 1440
uuucuagaga accaucagau guuuccaggg ugccccaagg accugaaaug acccugugcc 1500
uuauuugaac uaaccaauca guucgcuucu cgcuucuguu cgcgcgcuuc ugcuccccga 1560
gcucaauaaa agagcccaca accccucacu cggcgcgcca guccuccgau ugacugaguc 1620
gcccggguac ccguguaucc aauaaacccu cuugcaguug ca 1662
<210> 13
<211> 1475
<212> DNA
<213> 人工序列
<220>
<223> hCD19CAR1
<400> 13
gcggccgcat ggccctccct gtcaccgccc tgctgcttcc gctggctctt ctgctccacg 60
ccgctcggcc cgaaattgtg atgacccagt cacccgccac tcttagcctt tcacccggtg 120
agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt aattggtatc 180
aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg ctccattctg 240
gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc actatcagct 300
cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc ctgccctaca 360
cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga ggaggtgggt 420
ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt gtgaagccat 480
cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat tacggggtgt 540
cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt tggggctctg 600
agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag gacaactcta 660
agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc gtgtactatt 720
gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga cagggtactc 780
tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg gctcctacca 840
tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct ggtggggccg 900
tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct ctggctggta 960
cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc ggtcggaaga 1020
agctgctgta catctttaag caacccttca tgaggcctgt gcagactact caagaggagg 1080
acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg cgcgtgaaat 1140
tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc tacaacgaac 1200
tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga cgggacccag 1260
aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac gagctccaaa 1320
aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc agaagaggca 1380
aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc tatgacgctc 1440
ttcacatgca ggccctgccg cctcggtagg tcgac 1475
<210> 14
<211> 1475
<212> DNA
<213> 人工序列
<220>
<223> hCD19CAR2
<400> 14
gcggccgcat ggccctccct gtcaccgccc tgctgcttcc gctggctctt ctgctccacg 60
ccgctcggcc cgaaattgtg atgacccagt cacccgccac tcttagcctt tcacccggtg 120
agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt aattggtatc 180
aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg ctccattctg 240
gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc actatcagct 300
cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc ctgccctaca 360
cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga ggaggtgggt 420
ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt gtgaagccat 480
cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat tacggggtgt 540
cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt tggggctctg 600
agactactta ctaccaatca tccctcaagt cacgcgtcac catctcaaag gacaactcta 660
agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc gtgtactatt 720
gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga cagggtactc 780
tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg gctcctacca 840
tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct ggtggggccg 900
tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct ctggctggta 960
cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc ggtcggaaga 1020
agctgctgta catctttaag caacccttca tgaggcctgt gcagactact caagaggagg 1080
acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg cgcgtgaaat 1140
tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc tacaacgaac 1200
tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga cgggacccag 1260
aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac gagctccaaa 1320
aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc agaagaggca 1380
aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc tatgacgctc 1440
ttcacatgca ggccctgccg cctcggtagg tcgac 1475
<210> 15
<211> 1490
<212> DNA
<213> 人工序列
<220>
<223> hCD19CAR3
<400> 15
gcggccgcat ggccctccct gtcaccgccc tgctgcttcc gctggctctt ctgctccacg 60
ccgctcggcc cgaaattgtg atgacccagt cacccgccac tcttagcctt tcacccggtg 120
agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt aattggtatc 180
aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg ctccattctg 240
gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc actatcagct 300
cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc ctgccctaca 360
cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga ggaggtgggt 420
ccggcggtgg aggaagcgga ggcggtggga gccaggtcca actccaagaa agcggaccgg 480
gtcttgtgaa gccatcagaa actctttcac tgacttgtac tgtgagcgga gtgtctctcc 540
ccgattacgg ggtgtcttgg atcagacagc caccggggaa gggtctggaa tggattggag 600
tgatttgggg ctctgagact acttactaca actcatccct caagtcacgc gtcaccatct 660
caaaggacaa ctctaagaat caggtgtcac tgaaactgtc atctgtgacc gcagccgaca 720
ccgccgtgta ctattgcgct aagcattact attatggcgg gagctacgca atggattact 780
ggggacaggg tactctggtc accgtgtcca gcaccactac cccagcaccg aggccaccca 840
ccccggctcc taccatcgcc tcccagcctc tgtccctgcg tccggaggca tgtagacccg 900
cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc tacatttggg 960
cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact ctttactgta 1020
agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga 1080
ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg 1140
aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag gggcagaacc 1200
agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg gacaagcgga 1260
gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt 1320
acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt atgaaagggg 1380
aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc gccaccaagg 1440
acacctatga cgctcttcac atgcaggccc tgccgcctcg gtaggtcgac 1490
<210> 16
<211> 1490
<212> DNA
<213> 人工序列
<220>
<223> hCD19CAR4
<400> 16
gcggccgcat ggctctgccc gtgaccgcac tcctcctgcc actggctctg ctgcttcacg 60
ccgctcgccc acaagtccag cttcaagaat cagggcctgg tctggtgaag ccatctgaga 120
ctctgtccct cacttgcacc gtgagcggag tgtccctccc agactacgga gtgagctgga 180
ttagacagcc tcccggaaag ggactggagt ggatcggagt gatttggggt agcgaaacca 240
cttactataa ctcttccctg aagtcacggg tcaccatttc aaaggataac tcaaagaatc 300
aagtgagcct caagctctca tcagtcaccg ccgctgacac cgccgtgtat tactgtgcca 360
agcattacta ctatggaggg tcctacgcca tggactactg gggccaggga actctggtca 420
ctgtgtcatc tggtggagga ggtagcggag gaggcgggag cggtggaggt ggctccggag 480
gtggcggaag cgaaatcgtg atgacccaga gccctgcaac cctgtccctt tctcccgggg 540
aacgggctac cctttcttgt cgggcatcac aagatatctc aaaatacctc aattggtatc 600
aacagaagcc gggacaggcc cctaggcttc ttatctacca cacctctcgc ctgcatagcg 660
ggattcccgc acgctttagc gggtctggaa gcgggaccga ctacactctg accatctcat 720
ctctccagcc cgaggacttc gccgtctact tctgccagca gggtaacacc ctgccgtaca 780
ccttcggcca gggcaccaag cttgagatca aaaccactac tcccgctcca aggccaccca 840
cccctgcccc gaccatcgcc tctcagccgc tttccctgcg tccggaggca tgtagacccg 900
cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc tacatttggg 960
cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact ctttactgta 1020
agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga 1080
ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg 1140
aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag gggcagaacc 1200
agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg gacaagcgga 1260
gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt 1320
acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt atgaaagggg 1380
aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc gccaccaagg 1440
acacctatga cgctcttcac atgcaggccc tgccgcctcg gtaggtcgac 1490
<210> 17
<211> 1475
<212> DNA
<213> 人工序列
<220>
<223> hCD19CAR5
<400> 17
gcggccgcat ggccttacca gtgaccgcct tgctcctgcc gctggccttg ctgctccacg 60
ccgccaggcc ggacatccag atgacacaga ctacatcctc cctgtctgcc tctctgggag 120
acagagtcac catcagttgc agggcaagtc aggacattag taaatattta aattggtatc 180
agcagaaacc agatggaact gttaaactcc tgatctacca tacatcaaga ttacactcag 240
gagtcccatc aaggttcagt ggcagtgggt ctggaacaga ttattctctc accattagca 300
acctggagca agaagatatt gccacttact tttgccaaca gggtaatacg cttccgtaca 360
cgttcggagg ggggaccaag ctggagatca caggtggcgg tggctcgggc ggtggtgggt 420
cgggtggcgg cggatctgag gtgaaactgc aggagtcagg acctggcctg gtggcgccct 480
cacagagcct gtccgtcaca tgcactgtct caggggtctc attacccgac tatggtgtaa 540
gctggattcg ccagcctcca cgaaagggtc tggagtggct gggagtaata tggggtagtg 600
aaaccacata ctataattca gctctcaaat ccagactgac catcatcaag gacaactcca 660
agagccaagt tttcttaaaa atgaacagtc tgcaaactga tgacacagcc atttactact 720
gtgccaaaca ttattactac ggtggtagct atgctatgga ctactggggc caaggaacct 780
cagtcaccgt ctcctcaacc acgacgccag cgccgcgacc accaacaccg gcgcccacca 840
tcgcgtcgca gcccctgtcc ctgcgcccag aggcgtgccg gccagcggcg gggggcgcag 900
tgcacacgag ggggctggac ttcgcctgtg atatctacat ctgggcgccc ttggccggga 960
cttgtggggt ccttctcctg tcactggtta tcacccttta ctgcaaacgg ggcagaaaga 1020
aactcctgta tatattcaaa caaccattta tgagaccagt acaaactact caagaggaag 1080
atggctgtag ctgccgattt ccagaagaag aagaaggagg atgtgaactg agagtgaagt 1140
tcagcaggag cgcagacgcc cccgcgtaca agcagggcca gaaccagctc tataacgagc 1200
tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc cgggaccctg 1260
agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat gaactgcaga 1320
aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc cggaggggca 1380
aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc tacgacgccc 1440
ttcacatgca ggccctgccc cctcgctagg tcgac 1475
<210> 18
<211> 6287
<212> DNA
<213> 人工序列
<220>
<223> pBA9b-hCD19CAR1
<400> 18
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgcatggc cctccctgtc accgccctgc tgcttccgct ggctcttctg ctccacgccg 1980
ctcggcccga aattgtgatg acccagtcac ccgccactct tagcctttca cccggtgagc 2040
gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat tggtatcaac 2100
agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc cattctggaa 2160
tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact atcagctcac 2220
tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg ccctacacct 2280
ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga ggtgggtccg 2340
gcggtggagg aagccaggtc caactccaag aaagcggacc gggtcttgtg aagccatcag 2400
aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac ggggtgtctt 2460
ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg ggctctgaga 2520
ctacttacta ctcttcatcc ctcaagtcac gcgtcaccat ctcaaaggac aactctaaga 2580
atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg tactattgcg 2640
ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag ggtactctgg 2700
tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct cctaccatcg 2760
cctcccagcc tctgtccctg cgtccggagg catgtagacc cgcagctggt ggggccgtgc 2820
atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg gctggtactt 2880
gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt cggaagaagc 2940
tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa gaggaggacg 3000
gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc gtgaaattca 3060
gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac aacgaactca 3120
atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg gacccagaaa 3180
tgggcgggaa gccgcgcaga aagaatcccc aagagggcct gtacaacgag ctccaaaagg 3240
ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga agaggcaaag 3300
gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat gacgctcttc 3360
acatgcaggc cctgccgcct cggtaggtcg acaagcttgg atccatcgat aaaataaaag 3420
attttattta gtctccagaa aaagggggga atgaaagacc ccacctgtag gtttggcaag 3480
ctagcttaag taacgccatt ttgcaaggca tggaaaaata cataactgag aatagagaag 3540
ttcagatcaa ggtcaggaac agatggaaca gctgaatatg ggccaaacag gatatctgtg 3600
gtaagcagtt cctgccccgg ctcagggcca agaacagatg gaacagctga atatgggcca 3660
aacaggatat ctgtggtaag cagttcctgc cccggctcag ggccaagaac agatggtccc 3720
cagatgcggt ccagccctca gcagtttcta gagaaccatc agatgtttcc agggtgcccc 3780
aaggacctga aatgaccctg tgccttattt gaactaacca atcagttcgc ttctcgcttc 3840
tgttcgcgcg cttctgctcc ccgagctcaa taaaagagcc cacaacccct cactcggcgc 3900
gccagtcctc cgattgactg agtcgcccgg gtacccgtgt atccaataaa ccctcttgca 3960
gttgcatccg acttgtggtc tcgctgttcc ttgggagggt ctcctctgag tgattgacta 4020
cccgtcagcg ggggtctttc atttgaagcc gaattcgtaa tcatggtcat agctgtttcc 4080
tgtgtgaaat tgttatccgc tcacaattcc acacaacata cgagccggaa gcataaagtg 4140
taaagcctgg ggtgcctaat gagtgagcta actcacatta attgcgttgc gctcactgcc 4200
cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg 4260
gagaggcggt ttgcgtattg ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc 4320
ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac ggttatccac 4380
agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa 4440
ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg acgagcatca 4500
caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa gataccaggc 4560
gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata 4620
cctgtccgcc tttctccctt cgggaagcgt ggcgctttct caaagctcac gctgtaggta 4680
tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca 4740
gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga 4800
cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg 4860
tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa cagtatttgg 4920
tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg 4980
caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag 5040
aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg ctcagtggaa 5100
cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct tcacctagat 5160
ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt aaacttggtc 5220
tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc tatttcgttc 5280
atccatagtt gcctgactcc ccgtcgtgta gataactacg atacgggagg gcttaccatc 5340
tggccccagt gctgcaatga taccgcgaga cccacgctca ccggctccag atttatcagc 5400
aataaaccag ccagccggaa gggccgagcg cagaagtggt cctgcaactt tatccgcctc 5460
catccagtct attaattgtt gccgggaagc tagagtaagt agttcgccag ttaatagttt 5520
gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc 5580
ttcattcagc tccggttccc aacgatcaag gcgagttaca tgatccccca tgttgtgcaa 5640
aaaagcggtt agctccttcg gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt 5700
atcactcatg gttatggcag cactgcataa ttctcttact gtcatgccat ccgtaagatg 5760
cttttctgtg actggtgagt actcaaccaa gtcattctga gaatagtgta tgcggcgacc 5820
gagttgctct tgcccggcgt caatacggga taataccgcg ccacatagca gaactttaaa 5880
agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct taccgctgtt 5940
gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat cttttacttt 6000
caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa agggaataag 6060
ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt gaagcattta 6120
tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa ataaacaaat 6180
aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa ccattattat 6240
catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtc 6287
<210> 19
<211> 6287
<212> DNA
<213> 人工序列
<220>
<223> pBA9b-hCD19CAR2
<400> 19
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgcatggc cctccctgtc accgccctgc tgcttccgct ggctcttctg ctccacgccg 1980
ctcggcccga aattgtgatg acccagtcac ccgccactct tagcctttca cccggtgagc 2040
gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat tggtatcaac 2100
agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc cattctggaa 2160
tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact atcagctcac 2220
tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg ccctacacct 2280
ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga ggtgggtccg 2340
gcggtggagg aagccaggtc caactccaag aaagcggacc gggtcttgtg aagccatcag 2400
aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac ggggtgtctt 2460
ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg ggctctgaga 2520
ctacttacta ccaatcatcc ctcaagtcac gcgtcaccat ctcaaaggac aactctaaga 2580
atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg tactattgcg 2640
ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag ggtactctgg 2700
tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct cctaccatcg 2760
cctcccagcc tctgtccctg cgtccggagg catgtagacc cgcagctggt ggggccgtgc 2820
atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg gctggtactt 2880
gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt cggaagaagc 2940
tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa gaggaggacg 3000
gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc gtgaaattca 3060
gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac aacgaactca 3120
atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg gacccagaaa 3180
tgggcgggaa gccgcgcaga aagaatcccc aagagggcct gtacaacgag ctccaaaagg 3240
ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga agaggcaaag 3300
gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat gacgctcttc 3360
acatgcaggc cctgccgcct cggtaggtcg acaagcttgg atccatcgat aaaataaaag 3420
attttattta gtctccagaa aaagggggga atgaaagacc ccacctgtag gtttggcaag 3480
ctagcttaag taacgccatt ttgcaaggca tggaaaaata cataactgag aatagagaag 3540
ttcagatcaa ggtcaggaac agatggaaca gctgaatatg ggccaaacag gatatctgtg 3600
gtaagcagtt cctgccccgg ctcagggcca agaacagatg gaacagctga atatgggcca 3660
aacaggatat ctgtggtaag cagttcctgc cccggctcag ggccaagaac agatggtccc 3720
cagatgcggt ccagccctca gcagtttcta gagaaccatc agatgtttcc agggtgcccc 3780
aaggacctga aatgaccctg tgccttattt gaactaacca atcagttcgc ttctcgcttc 3840
tgttcgcgcg cttctgctcc ccgagctcaa taaaagagcc cacaacccct cactcggcgc 3900
gccagtcctc cgattgactg agtcgcccgg gtacccgtgt atccaataaa ccctcttgca 3960
gttgcatccg acttgtggtc tcgctgttcc ttgggagggt ctcctctgag tgattgacta 4020
cccgtcagcg ggggtctttc atttgaagcc gaattcgtaa tcatggtcat agctgtttcc 4080
tgtgtgaaat tgttatccgc tcacaattcc acacaacata cgagccggaa gcataaagtg 4140
taaagcctgg ggtgcctaat gagtgagcta actcacatta attgcgttgc gctcactgcc 4200
cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg 4260
gagaggcggt ttgcgtattg ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc 4320
ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac ggttatccac 4380
agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa 4440
ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg acgagcatca 4500
caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa gataccaggc 4560
gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata 4620
cctgtccgcc tttctccctt cgggaagcgt ggcgctttct caaagctcac gctgtaggta 4680
tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca 4740
gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga 4800
cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg 4860
tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa cagtatttgg 4920
tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg 4980
caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag 5040
aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg ctcagtggaa 5100
cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct tcacctagat 5160
ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt aaacttggtc 5220
tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc tatttcgttc 5280
atccatagtt gcctgactcc ccgtcgtgta gataactacg atacgggagg gcttaccatc 5340
tggccccagt gctgcaatga taccgcgaga cccacgctca ccggctccag atttatcagc 5400
aataaaccag ccagccggaa gggccgagcg cagaagtggt cctgcaactt tatccgcctc 5460
catccagtct attaattgtt gccgggaagc tagagtaagt agttcgccag ttaatagttt 5520
gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc 5580
ttcattcagc tccggttccc aacgatcaag gcgagttaca tgatccccca tgttgtgcaa 5640
aaaagcggtt agctccttcg gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt 5700
atcactcatg gttatggcag cactgcataa ttctcttact gtcatgccat ccgtaagatg 5760
cttttctgtg actggtgagt actcaaccaa gtcattctga gaatagtgta tgcggcgacc 5820
gagttgctct tgcccggcgt caatacggga taataccgcg ccacatagca gaactttaaa 5880
agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct taccgctgtt 5940
gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat cttttacttt 6000
caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa agggaataag 6060
ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt gaagcattta 6120
tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa ataaacaaat 6180
aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa ccattattat 6240
catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtc 6287
<210> 20
<211> 6302
<212> DNA
<213> 人工序列
<220>
<223> pBA9b-hCD19CAR3
<400> 20
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgcatggc cctccctgtc accgccctgc tgcttccgct ggctcttctg ctccacgccg 1980
ctcggcccga aattgtgatg acccagtcac ccgccactct tagcctttca cccggtgagc 2040
gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat tggtatcaac 2100
agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc cattctggaa 2160
tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact atcagctcac 2220
tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg ccctacacct 2280
ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga ggtgggtccg 2340
gcggtggagg aagcggaggc ggtgggagcc aggtccaact ccaagaaagc ggaccgggtc 2400
ttgtgaagcc atcagaaact ctttcactga cttgtactgt gagcggagtg tctctccccg 2460
attacggggt gtcttggatc agacagccac cggggaaggg tctggaatgg attggagtga 2520
tttggggctc tgagactact tactacaact catccctcaa gtcacgcgtc accatctcaa 2580
aggacaactc taagaatcag gtgtcactga aactgtcatc tgtgaccgca gccgacaccg 2640
ccgtgtacta ttgcgctaag cattactatt atggcgggag ctacgcaatg gattactggg 2700
gacagggtac tctggtcacc gtgtccagca ccactacccc agcaccgagg ccacccaccc 2760
cggctcctac catcgcctcc cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag 2820
ctggtggggc cgtgcatacc cggggtcttg acttcgcctg cgatatctac atttgggccc 2880
ctctggctgg tacttgcggg gtcctgctgc tttcactcgt gatcactctt tactgtaagc 2940
gcggtcggaa gaagctgctg tacatcttta agcaaccctt catgaggcct gtgcagacta 3000
ctcaagagga ggacggctgt tcatgccggt tcccagagga ggaggaaggc ggctgcgaac 3060
tgcgcgtgaa attcagccgc agcgcagatg ctccagccta caagcagggg cagaaccagc 3120
tctacaacga actcaatctt ggtcggagag aggagtacga cgtgctggac aagcggagag 3180
gacgggaccc agaaatgggc gggaagccgc gcagaaagaa tccccaagag ggcctgtaca 3240
acgagctcca aaaggataag atggcagaag cctatagcga gattggtatg aaaggggaac 3300
gcagaagagg caaaggccac gacggactgt accagggact cagcaccgcc accaaggaca 3360
cctatgacgc tcttcacatg caggccctgc cgcctcggta ggtcgacaag cttggatcca 3420
tcgataaaat aaaagatttt atttagtctc cagaaaaagg ggggaatgaa agaccccacc 3480
tgtaggtttg gcaagctagc ttaagtaacg ccattttgca aggcatggaa aaatacataa 3540
ctgagaatag agaagttcag atcaaggtca ggaacagatg gaacagctga atatgggcca 3600
aacaggatat ctgtggtaag cagttcctgc cccggctcag ggccaagaac agatggaaca 3660
gctgaatatg ggccaaacag gatatctgtg gtaagcagtt cctgccccgg ctcagggcca 3720
agaacagatg gtccccagat gcggtccagc cctcagcagt ttctagagaa ccatcagatg 3780
tttccagggt gccccaagga cctgaaatga ccctgtgcct tatttgaact aaccaatcag 3840
ttcgcttctc gcttctgttc gcgcgcttct gctccccgag ctcaataaaa gagcccacaa 3900
cccctcactc ggcgcgccag tcctccgatt gactgagtcg cccgggtacc cgtgtatcca 3960
ataaaccctc ttgcagttgc atccgacttg tggtctcgct gttccttggg agggtctcct 4020
ctgagtgatt gactacccgt cagcgggggt ctttcatttg aagccgaatt cgtaatcatg 4080
gtcatagctg tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc 4140
cggaagcata aagtgtaaag cctggggtgc ctaatgagtg agctaactca cattaattgc 4200
gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat 4260
cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac 4320
tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt 4380
aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca 4440
gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc 4500
ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact 4560
ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct 4620
gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcaaag 4680
ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca 4740
cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa 4800
cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc 4860
gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag 4920
aagaacagta tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg 4980
tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca 5040
gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 5100
tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 5160
gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 5220
tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat 5280
ctgtctattt cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg 5340
ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc 5400
tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc 5460
aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc 5520
gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc 5580
gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc 5640
ccccatgttg tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa 5700
gttggccgca gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat 5760
gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata 5820
gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca 5880
tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag 5940
gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc 6000
agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc 6060
aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata 6120
ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta 6180
gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtcta 6240
agaaaccatt attatcatga cattaaccta taaaaatagg cgtatcacga ggccctttcg 6300
tc 6302
<210> 21
<211> 6302
<212> DNA
<213> 人工序列
<220>
<223> pBA9b-hCD19CAR4
<400> 21
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgcatggc tctgcccgtg accgcactcc tcctgccact ggctctgctg cttcacgccg 1980
ctcgcccaca agtccagctt caagaatcag ggcctggtct ggtgaagcca tctgagactc 2040
tgtccctcac ttgcaccgtg agcggagtgt ccctcccaga ctacggagtg agctggatta 2100
gacagcctcc cggaaaggga ctggagtgga tcggagtgat ttggggtagc gaaaccactt 2160
actataactc ttccctgaag tcacgggtca ccatttcaaa ggataactca aagaatcaag 2220
tgagcctcaa gctctcatca gtcaccgccg ctgacaccgc cgtgtattac tgtgccaagc 2280
attactacta tggagggtcc tacgccatgg actactgggg ccagggaact ctggtcactg 2340
tgtcatctgg tggaggaggt agcggaggag gcgggagcgg tggaggtggc tccggaggtg 2400
gcggaagcga aatcgtgatg acccagagcc ctgcaaccct gtccctttct cccggggaac 2460
gggctaccct ttcttgtcgg gcatcacaag atatctcaaa atacctcaat tggtatcaac 2520
agaagccggg acaggcccct aggcttctta tctaccacac ctctcgcctg catagcggga 2580
ttcccgcacg ctttagcggg tctggaagcg ggaccgacta cactctgacc atctcatctc 2640
tccagcccga ggacttcgcc gtctacttct gccagcaggg taacaccctg ccgtacacct 2700
tcggccaggg caccaagctt gagatcaaaa ccactactcc cgctccaagg ccacccaccc 2760
ctgccccgac catcgcctct cagccgcttt ccctgcgtcc ggaggcatgt agacccgcag 2820
ctggtggggc cgtgcatacc cggggtcttg acttcgcctg cgatatctac atttgggccc 2880
ctctggctgg tacttgcggg gtcctgctgc tttcactcgt gatcactctt tactgtaagc 2940
gcggtcggaa gaagctgctg tacatcttta agcaaccctt catgaggcct gtgcagacta 3000
ctcaagagga ggacggctgt tcatgccggt tcccagagga ggaggaaggc ggctgcgaac 3060
tgcgcgtgaa attcagccgc agcgcagatg ctccagccta caagcagggg cagaaccagc 3120
tctacaacga actcaatctt ggtcggagag aggagtacga cgtgctggac aagcggagag 3180
gacgggaccc agaaatgggc gggaagccgc gcagaaagaa tccccaagag ggcctgtaca 3240
acgagctcca aaaggataag atggcagaag cctatagcga gattggtatg aaaggggaac 3300
gcagaagagg caaaggccac gacggactgt accagggact cagcaccgcc accaaggaca 3360
cctatgacgc tcttcacatg caggccctgc cgcctcggta ggtcgacaag cttggatcca 3420
tcgataaaat aaaagatttt atttagtctc cagaaaaagg ggggaatgaa agaccccacc 3480
tgtaggtttg gcaagctagc ttaagtaacg ccattttgca aggcatggaa aaatacataa 3540
ctgagaatag agaagttcag atcaaggtca ggaacagatg gaacagctga atatgggcca 3600
aacaggatat ctgtggtaag cagttcctgc cccggctcag ggccaagaac agatggaaca 3660
gctgaatatg ggccaaacag gatatctgtg gtaagcagtt cctgccccgg ctcagggcca 3720
agaacagatg gtccccagat gcggtccagc cctcagcagt ttctagagaa ccatcagatg 3780
tttccagggt gccccaagga cctgaaatga ccctgtgcct tatttgaact aaccaatcag 3840
ttcgcttctc gcttctgttc gcgcgcttct gctccccgag ctcaataaaa gagcccacaa 3900
cccctcactc ggcgcgccag tcctccgatt gactgagtcg cccgggtacc cgtgtatcca 3960
ataaaccctc ttgcagttgc atccgacttg tggtctcgct gttccttggg agggtctcct 4020
ctgagtgatt gactacccgt cagcgggggt ctttcatttg aagccgaatt cgtaatcatg 4080
gtcatagctg tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc 4140
cggaagcata aagtgtaaag cctggggtgc ctaatgagtg agctaactca cattaattgc 4200
gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat 4260
cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac 4320
tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt 4380
aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca 4440
gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc 4500
ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact 4560
ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct 4620
gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcaaag 4680
ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca 4740
cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa 4800
cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc 4860
gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag 4920
aagaacagta tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg 4980
tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca 5040
gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 5100
tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 5160
gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 5220
tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat 5280
ctgtctattt cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg 5340
ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc 5400
tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc 5460
aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc 5520
gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc 5580
gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc 5640
ccccatgttg tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa 5700
gttggccgca gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat 5760
gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata 5820
gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca 5880
tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag 5940
gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc 6000
agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc 6060
aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata 6120
ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta 6180
gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtcta 6240
agaaaccatt attatcatga cattaaccta taaaaatagg cgtatcacga ggccctttcg 6300
tc 6302
<210> 22
<211> 6287
<212> DNA
<213> 人工序列
<220>
<223> pBA9b-hCD19CAR5
<400> 22
tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60
cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120
ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180
accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240
attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300
tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360
tttcccagtc acgacgttgt aaaacgacgg ccagtgccaa gctgactcta gaggatcgat 420
ccccggccgc tctagcttaa gtaacgccat tttgcaaggc atggaaaaat acataactga 480
gaatagagaa gttcagatca aggtcaggaa cagatggaac agctgaatat gggccaaaca 540
ggatatctgt ggtaagcagt tcctgccccg gctcagggcc aagaacagat ggaacagctg 600
aatatgggcc aaacaggata tctgtggtaa gcagttcctg ccccggctca gggccaagaa 660
cagatggtcc ccagatgcgg tccagccctc agcagtttct agagaaccat cagatgtttc 720
cagggtgccc caaggacctg aaatgaccct gtgccttatt tgaactaacc aatcagttcg 780
cttctcgctt ctgttcgcgc gcttctgctc cccgagctca ataaaagagc ccacaacccc 840
tcactcggcg cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa 900
accctcttgc agttgcatcc gacttgtggt ctcgctgttc cttgggaggg tctcctctga 960
gtgattgact acccgtcagc gggggtcttt catttggggg ctcgtccggg atcgggagac 1020
ccctgcccag ggaccaccga cccaccaccg ggaggtaagc tggccagcaa cttatctgtg 1080
tctgtccgat tgtctagtgt ctatgactga ttttatgcgc ctgcgtcggt actagttagc 1140
taactagctc tgtatctggc ggacccgtgg tggaactgac gagttcggaa cacccggccg 1200
caaccctggg agacgtccca gggacttcgg gggccgtttt tgtggcccga cctgagtcca 1260
aaaatcccga tcgttttgga ctctttggtg cacccccctt agaggaggga tatgtggttc 1320
tggtaggaga cgagaaccta aaacagttcc cgcctccgtc tgaatttttg ctttcggttt 1380
gggaccgaag ccgcgccgcg cgtcttgtct gctgcagcat cgttctgtgt tgtctctgtc 1440
tgactgtgtt tctgtatttg tctgagaatt aaggccagac tgttaccact ccctgaagtt 1500
tgaccttagg tcactggaaa gatgtcgagc ggatcgctca caaccagtcg gtagatgtca 1560
agaagagacg ttgggttacc ttctgctctg cagaatggcc aacctttaac gtcggatggc 1620
cgcgagacgg cacctttaac cgagacctca tcacccaggt taagatcaag gtcttttcac 1680
ctggcccgca tggacaccca gaccaggtcc cctacatcgt gacctgggaa gccttggctt 1740
ttgacccccc tccctgggtc aagccctttg tacaccctaa gcctccgcct cctcttcctc 1800
catccgcccc gtctctcccc cttgaacctc ctcgttcgac cccgcctcga tcctcccttt 1860
atccagccct cactccttct ctaggcgccg gaattaattc tcgaggggcc cagatctgcg 1920
gccgcatggc cttaccagtg accgccttgc tcctgccgct ggccttgctg ctccacgccg 1980
ccaggccgga catccagatg acacagacta catcctccct gtctgcctct ctgggagaca 2040
gagtcaccat cagttgcagg gcaagtcagg acattagtaa atatttaaat tggtatcagc 2100
agaaaccaga tggaactgtt aaactcctga tctaccatac atcaagatta cactcaggag 2160
tcccatcaag gttcagtggc agtgggtctg gaacagatta ttctctcacc attagcaacc 2220
tggagcaaga agatattgcc acttactttt gccaacaggg taatacgctt ccgtacacgt 2280
tcggaggggg gaccaagctg gagatcacag gtggcggtgg ctcgggcggt ggtgggtcgg 2340
gtggcggcgg atctgaggtg aaactgcagg agtcaggacc tggcctggtg gcgccctcac 2400
agagcctgtc cgtcacatgc actgtctcag gggtctcatt acccgactat ggtgtaagct 2460
ggattcgcca gcctccacga aagggtctgg agtggctggg agtaatatgg ggtagtgaaa 2520
ccacatacta taattcagct ctcaaatcca gactgaccat catcaaggac aactccaaga 2580
gccaagtttt cttaaaaatg aacagtctgc aaactgatga cacagccatt tactactgtg 2640
ccaaacatta ttactacggt ggtagctatg ctatggacta ctggggccaa ggaacctcag 2700
tcaccgtctc ctcaaccacg acgccagcgc cgcgaccacc aacaccggcg cccaccatcg 2760
cgtcgcagcc cctgtccctg cgcccagagg cgtgccggcc agcggcgggg ggcgcagtgc 2820
acacgagggg gctggacttc gcctgtgata tctacatctg ggcgcccttg gccgggactt 2880
gtggggtcct tctcctgtca ctggttatca ccctttactg caaacggggc agaaagaaac 2940
tcctgtatat attcaaacaa ccatttatga gaccagtaca aactactcaa gaggaagatg 3000
gctgtagctg ccgatttcca gaagaagaag aaggaggatg tgaactgaga gtgaagttca 3060
gcaggagcgc agacgccccc gcgtacaagc agggccagaa ccagctctat aacgagctca 3120
atctaggacg aagagaggag tacgatgttt tggacaagag acgtggccgg gaccctgaga 3180
tggggggaaa gccgagaagg aagaaccctc aggaaggcct gtacaatgaa ctgcagaaag 3240
ataagatggc ggaggcctac agtgagattg ggatgaaagg cgagcgccgg aggggcaagg 3300
ggcacgatgg cctttaccag ggtctcagta cagccaccaa ggacacctac gacgcccttc 3360
acatgcaggc cctgccccct cgctaggtcg acaagcttgg atccatcgat aaaataaaag 3420
attttattta gtctccagaa aaagggggga atgaaagacc ccacctgtag gtttggcaag 3480
ctagcttaag taacgccatt ttgcaaggca tggaaaaata cataactgag aatagagaag 3540
ttcagatcaa ggtcaggaac agatggaaca gctgaatatg ggccaaacag gatatctgtg 3600
gtaagcagtt cctgccccgg ctcagggcca agaacagatg gaacagctga atatgggcca 3660
aacaggatat ctgtggtaag cagttcctgc cccggctcag ggccaagaac agatggtccc 3720
cagatgcggt ccagccctca gcagtttcta gagaaccatc agatgtttcc agggtgcccc 3780
aaggacctga aatgaccctg tgccttattt gaactaacca atcagttcgc ttctcgcttc 3840
tgttcgcgcg cttctgctcc ccgagctcaa taaaagagcc cacaacccct cactcggcgc 3900
gccagtcctc cgattgactg agtcgcccgg gtacccgtgt atccaataaa ccctcttgca 3960
gttgcatccg acttgtggtc tcgctgttcc ttgggagggt ctcctctgag tgattgacta 4020
cccgtcagcg ggggtctttc atttgaagcc gaattcgtaa tcatggtcat agctgtttcc 4080
tgtgtgaaat tgttatccgc tcacaattcc acacaacata cgagccggaa gcataaagtg 4140
taaagcctgg ggtgcctaat gagtgagcta actcacatta attgcgttgc gctcactgcc 4200
cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg 4260
gagaggcggt ttgcgtattg ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc 4320
ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag gcggtaatac ggttatccac 4380
agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa 4440
ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg acgagcatca 4500
caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa gataccaggc 4560
gtttccccct ggaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata 4620
cctgtccgcc tttctccctt cgggaagcgt ggcgctttct caaagctcac gctgtaggta 4680
tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca 4740
gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga 4800
cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg 4860
tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa cagtatttgg 4920
tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg 4980
caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag 5040
aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg ctcagtggaa 5100
cgaaaactca cgttaaggga ttttggtcat gagattatca aaaaggatct tcacctagat 5160
ccttttaaat taaaaatgaa gttttaaatc aatctaaagt atatatgagt aaacttggtc 5220
tgacagttac caatgcttaa tcagtgaggc acctatctca gcgatctgtc tatttcgttc 5280
atccatagtt gcctgactcc ccgtcgtgta gataactacg atacgggagg gcttaccatc 5340
tggccccagt gctgcaatga taccgcgaga cccacgctca ccggctccag atttatcagc 5400
aataaaccag ccagccggaa gggccgagcg cagaagtggt cctgcaactt tatccgcctc 5460
catccagtct attaattgtt gccgggaagc tagagtaagt agttcgccag ttaatagttt 5520
gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc 5580
ttcattcagc tccggttccc aacgatcaag gcgagttaca tgatccccca tgttgtgcaa 5640
aaaagcggtt agctccttcg gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt 5700
atcactcatg gttatggcag cactgcataa ttctcttact gtcatgccat ccgtaagatg 5760
cttttctgtg actggtgagt actcaaccaa gtcattctga gaatagtgta tgcggcgacc 5820
gagttgctct tgcccggcgt caatacggga taataccgcg ccacatagca gaactttaaa 5880
agtgctcatc attggaaaac gttcttcggg gcgaaaactc tcaaggatct taccgctgtt 5940
gagatccagt tcgatgtaac ccactcgtgc acccaactga tcttcagcat cttttacttt 6000
caccagcgtt tctgggtgag caaaaacagg aaggcaaaat gccgcaaaaa agggaataag 6060
ggcgacacgg aaatgttgaa tactcatact cttccttttt caatattatt gaagcattta 6120
tcagggttat tgtctcatga gcggatacat atttgaatgt atttagaaaa ataaacaaat 6180
aggggttccg cgcacatttc cccgaaaagt gccacctgac gtctaagaaa ccattattat 6240
catgacatta acctataaaa ataggcgtat cacgaggccc tttcgtc 6287
<210> 23
<211> 288
<212> DNA
<213> 人工序列
<220>
<223> Adnectins (10Fn3)
<220>
<221> CDS
<222> (1)..(288)
<400> 23
gtg agc gac gtg ccc aga aag ctg gag gtg gtg gcc gcc acc ccc acc 48
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
agc ctg ctg atc agc tgg gac gcc ccc gcc gtg acc gtg aga tac tac 96
Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala Val Thr Val Arg Tyr Tyr
20 25 30
aga atc acc tac ggc gag acc ggc ggc aac agc ccc gtg cag gag ttc 144
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
acc gtg ccc ggc agc aag agc acc gcc acc atc agc ggc ctg aag ccc 192
Thr Val Pro Gly Ser Lys Ser Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
ggc gtg gac tac acc atc acc gtg tac gcc gtg acc ggc aga ggc gac 240
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Gly Arg Gly Asp
65 70 75 80
agc ccc gcc agc agc aag ccc atc agc aac tac aga acc gcc ctg gag 288
Ser Pro Ala Ser Ser Lys Pro Ile Ser Asn Tyr Arg Thr Ala Leu Glu
85 90 95
<210> 24
<211> 96
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 24
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala Val Thr Val Arg Tyr Tyr
20 25 30
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
Thr Val Pro Gly Ser Lys Ser Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Gly Arg Gly Asp
65 70 75 80
Ser Pro Ala Ser Ser Lys Pro Ile Ser Asn Tyr Arg Thr Ala Leu Glu
85 90 95
<210> 25
<211> 303
<212> DNA
<213> 人工序列
<220>
<223> Adnectin 1
<220>
<221> CDS
<222> (1)..(303)
<400> 25
gtg agc gac gtg ccc aga aag ctg gag gtg gtg gcc gcc acc ccc acc 48
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
agc ctg ctg atc agc tgg gac agc ggc aga ggc agc tac aga tac tac 96
Ser Leu Leu Ile Ser Trp Asp Ser Gly Arg Gly Ser Tyr Arg Tyr Tyr
20 25 30
aga atc acc tac ggc gag acc ggc ggc aac agc ccc gtg cag gag ttc 144
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
acc gtg ccc ggc ccc gtg cac acc gcc acc atc agc ggc ctg aag ccc 192
Thr Val Pro Gly Pro Val His Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
ggc gtg gac tac acc atc acc gtg tac gcc gtg acc gac cac aag ccc 240
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Asp His Lys Pro
65 70 75 80
cac gcc gac ggc ccc cac acc tac cac gag agc ccc atc agc aac tac 288
His Ala Asp Gly Pro His Thr Tyr His Glu Ser Pro Ile Ser Asn Tyr
85 90 95
aga acc gcc ctg gag 303
Arg Thr Ala Leu Glu
100
<210> 26
<211> 101
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 26
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
Ser Leu Leu Ile Ser Trp Asp Ser Gly Arg Gly Ser Tyr Arg Tyr Tyr
20 25 30
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
Thr Val Pro Gly Pro Val His Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Asp His Lys Pro
65 70 75 80
His Ala Asp Gly Pro His Thr Tyr His Glu Ser Pro Ile Ser Asn Tyr
85 90 95
Arg Thr Ala Leu Glu
100
<210> 27
<211> 288
<212> DNA
<213> 人工序列
<220>
<223> Adnectin 2
<220>
<221> CDS
<222> (1)..(288)
<400> 27
gtg agc gac gtg ccc aga aag ctg gag gtg gtg gcc gcc acc ccc acc 48
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
agc ctg ctg atc agc tgg gag cac gac tac ccc tac aga aga tac tac 96
Ser Leu Leu Ile Ser Trp Glu His Asp Tyr Pro Tyr Arg Arg Tyr Tyr
20 25 30
aga atc acc tac ggc gag acc ggc ggc aac agc ccc gtg cag gag ttc 144
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
acc gtg ccc aag gac gtg gac acc gcc acc atc agc ggc ctg aag ccc 192
Thr Val Pro Lys Asp Val Asp Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
ggc gtg gac tac acc atc acc gtg tac gcc gtg acc agc agc tac aag 240
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Ser Ser Tyr Lys
65 70 75 80
tac gac atg cag tac agc ccc atc agc aac tac aga acc gcc ctg gag 288
Tyr Asp Met Gln Tyr Ser Pro Ile Ser Asn Tyr Arg Thr Ala Leu Glu
85 90 95
<210> 28
<211> 96
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 28
Val Ser Asp Val Pro Arg Lys Leu Glu Val Val Ala Ala Thr Pro Thr
1 5 10 15
Ser Leu Leu Ile Ser Trp Glu His Asp Tyr Pro Tyr Arg Arg Tyr Tyr
20 25 30
Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe
35 40 45
Thr Val Pro Lys Asp Val Asp Thr Ala Thr Ile Ser Gly Leu Lys Pro
50 55 60
Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Ser Ser Tyr Lys
65 70 75 80
Tyr Asp Met Gln Tyr Ser Pro Ile Ser Asn Tyr Arg Thr Ala Leu Glu
85 90 95
<210> 29
<211> 276
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (1Fn3)
<220>
<221> CDS
<222> (1)..(276)
<400> 29
agc ggc ccc gtg gag gtg ttc atc acc gag acc ccc agc cag ccc aac 48
Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn
1 5 10 15
agc cac ccc atc cag tgg aac gcc ccc cag ccc agc cac atc agc aag 96
Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys
20 25 30
tac atc ctg aga tgg aga ccc aag aac agc gtg ggc aga tgg aag gag 144
Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu
35 40 45
gcc acc atc ccc ggc cac ctg aac agc tac acc atc aag ggc ctg aag 192
Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys
50 55 60
ccc ggc gtg gtg tac gag ggc cag ctg atc agc atc cag cag tac ggc 240
Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly
65 70 75 80
cac cag gag gtg acc aga ttc gac ttc acc acc acc 276
His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr
85 90
<210> 30
<211> 92
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 30
Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn
1 5 10 15
Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys
20 25 30
Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu
35 40 45
Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys
50 55 60
Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly
65 70 75 80
His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr
85 90
<210> 31
<211> 270
<212> DNA
<213> 人工序列
<220>
<223> Pronectins 2Fn3)
<220>
<221> CDS
<222> (1)..(270)
<400> 31
agc ccc ctg gtg gcc acc agc gag agc gtg acc gag atc acc gcc agc 48
Ser Pro Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser
1 5 10 15
agc ttc gtg gtg agc tgg gtg agc gcc agc gac acc gtg agc ggc ttc 96
Ser Phe Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe
20 25 30
aga gtg gag tac gag ctg agc gag gag ggc gac gag ccc cag tac ctg 144
Arg Val Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu
35 40 45
gac ctg ccc agc acc gcc acc agc gtg aac atc ccc gac ctg ctg ccc 192
Asp Leu Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro
50 55 60
ggc aga aag tac atc gtg aac gtg tac cag agc gag gac ggc gag cag 240
Gly Arg Lys Tyr Ile Val Asn Val Tyr Gln Ser Glu Asp Gly Glu Gln
65 70 75 80
agc ctg atc ctg agc acc agc cag acc acc 270
Ser Leu Ile Leu Ser Thr Ser Gln Thr Thr
85 90
<210> 32
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 32
Ser Pro Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser
1 5 10 15
Ser Phe Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe
20 25 30
Arg Val Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu
35 40 45
Asp Leu Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro
50 55 60
Gly Arg Lys Tyr Ile Val Asn Val Tyr Gln Ser Glu Asp Gly Glu Gln
65 70 75 80
Ser Leu Ile Leu Ser Thr Ser Gln Thr Thr
85 90
<210> 33
<211> 282
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (3Fn3)
<220>
<221> CDS
<222> (1)..(282)
<400> 33
gcc ccc gac gcc ccc ccc gac ccc acc gtg gac cag gtg gac gac acc 48
Ala Pro Asp Ala Pro Pro Asp Pro Thr Val Asp Gln Val Asp Asp Thr
1 5 10 15
agc atc gtg gtg aga tgg agc aga ccc cag gcc ccc atc acc ggc tac 96
Ser Ile Val Val Arg Trp Ser Arg Pro Gln Ala Pro Ile Thr Gly Tyr
20 25 30
aga atc gtg tac agc ccc agc gtg gag ggc agc agc acc gag ctg aac 144
Arg Ile Val Tyr Ser Pro Ser Val Glu Gly Ser Ser Thr Glu Leu Asn
35 40 45
ctg ccc gag acc gcc aac agc gtg acc ctg agc gac ctg cag ccc ggc 192
Leu Pro Glu Thr Ala Asn Ser Val Thr Leu Ser Asp Leu Gln Pro Gly
50 55 60
gtg cag tac aac atc acc atc tac gcc gtg gag gag aac cag gag agc 240
Val Gln Tyr Asn Ile Thr Ile Tyr Ala Val Glu Glu Asn Gln Glu Ser
65 70 75 80
acc ccc gtg gtg atc cag cag gag acc acc ggc acc ccc aga 282
Thr Pro Val Val Ile Gln Gln Glu Thr Thr Gly Thr Pro Arg
85 90
<210> 34
<211> 94
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 34
Ala Pro Asp Ala Pro Pro Asp Pro Thr Val Asp Gln Val Asp Asp Thr
1 5 10 15
Ser Ile Val Val Arg Trp Ser Arg Pro Gln Ala Pro Ile Thr Gly Tyr
20 25 30
Arg Ile Val Tyr Ser Pro Ser Val Glu Gly Ser Ser Thr Glu Leu Asn
35 40 45
Leu Pro Glu Thr Ala Asn Ser Val Thr Leu Ser Asp Leu Gln Pro Gly
50 55 60
Val Gln Tyr Asn Ile Thr Ile Tyr Ala Val Glu Glu Asn Gln Glu Ser
65 70 75 80
Thr Pro Val Val Ile Gln Gln Glu Thr Thr Gly Thr Pro Arg
85 90
<210> 35
<211> 270
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (4Fn3)
<220>
<221> CDS
<222> (1)..(270)
<400> 35
acc gtg ccc agc ccc aga gac ctg cag ttc gtg gag gtg acc gac gtg 48
Thr Val Pro Ser Pro Arg Asp Leu Gln Phe Val Glu Val Thr Asp Val
1 5 10 15
aag gtg acc atc atg tgg acc ccc ccc gag agc gcc gtg acc ggc tac 96
Lys Val Thr Ile Met Trp Thr Pro Pro Glu Ser Ala Val Thr Gly Tyr
20 25 30
aga gtg gac gtg atc ccc gtg aac ctg ccc ggc gag cac ggc cag aga 144
Arg Val Asp Val Ile Pro Val Asn Leu Pro Gly Glu His Gly Gln Arg
35 40 45
ctg ccc atc agc aga aac acc ttc gcc gag gtg acc ggc ctg agc ccc 192
Leu Pro Ile Ser Arg Asn Thr Phe Ala Glu Val Thr Gly Leu Ser Pro
50 55 60
ggc gtg acc tac tac ttc aag gtg ttc gcc gtg agc cac ggc aga gag 240
Gly Val Thr Tyr Tyr Phe Lys Val Phe Ala Val Ser His Gly Arg Glu
65 70 75 80
agc aag ccc ctg acc gcc cag cag acc acc 270
Ser Lys Pro Leu Thr Ala Gln Gln Thr Thr
85 90
<210> 36
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 36
Thr Val Pro Ser Pro Arg Asp Leu Gln Phe Val Glu Val Thr Asp Val
1 5 10 15
Lys Val Thr Ile Met Trp Thr Pro Pro Glu Ser Ala Val Thr Gly Tyr
20 25 30
Arg Val Asp Val Ile Pro Val Asn Leu Pro Gly Glu His Gly Gln Arg
35 40 45
Leu Pro Ile Ser Arg Asn Thr Phe Ala Glu Val Thr Gly Leu Ser Pro
50 55 60
Gly Val Thr Tyr Tyr Phe Lys Val Phe Ala Val Ser His Gly Arg Glu
65 70 75 80
Ser Lys Pro Leu Thr Ala Gln Gln Thr Thr
85 90
<210> 37
<211> 270
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (5Fn3)
<220>
<221> CDS
<222> (1)..(270)
<400> 37
aag ctg gac gcc ccc acc aac ctg cag ttc gtg aac gag acc gac agc 48
Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu Thr Asp Ser
1 5 10 15
acc gtg ctg gtg aga tgg acc ccc ccc aga gcc cag atc acc ggc tac 96
Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln Ile Thr Gly Tyr
20 25 30
aga ctg acc gtg ggc ctg acc aga aga ggc cag ccc aga cag tac aac 144
Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln Pro Arg Gln Tyr Asn
35 40 45
gtg ggc ccc agc gtg agc aag tac ccc ctg aga aac ctg cag ccc gcc 192
Val Gly Pro Ser Val Ser Lys Tyr Pro Leu Arg Asn Leu Gln Pro Ala
50 55 60
agc gag tac acc gtg agc ctg gtg gcc atc aag ggc aac cag gag agc 240
Ser Glu Tyr Thr Val Ser Leu Val Ala Ile Lys Gly Asn Gln Glu Ser
65 70 75 80
ccc aag gcc acc ggc gtg ttc acc acc ctg 270
Pro Lys Ala Thr Gly Val Phe Thr Thr Leu
85 90
<210> 38
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 38
Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu Thr Asp Ser
1 5 10 15
Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln Ile Thr Gly Tyr
20 25 30
Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln Pro Arg Gln Tyr Asn
35 40 45
Val Gly Pro Ser Val Ser Lys Tyr Pro Leu Arg Asn Leu Gln Pro Ala
50 55 60
Ser Glu Tyr Thr Val Ser Leu Val Ala Ile Lys Gly Asn Gln Glu Ser
65 70 75 80
Pro Lys Ala Thr Gly Val Phe Thr Thr Leu
85 90
<210> 39
<211> 258
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (6Fn3)
<220>
<221> CDS
<222> (1)..(258)
<400> 39
cag ccc ggc agc agc atc ccc ccc tac aac acc gag gtg acc gag acc 48
Gln Pro Gly Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val Thr Glu Thr
1 5 10 15
acc atc gtg atc acc tgg acc ccc gcc ccc aga ctg ggc ttc aag ctg 96
Thr Ile Val Ile Thr Trp Thr Pro Ala Pro Arg Leu Gly Phe Lys Leu
20 25 30
ggc gtg aga ccc agc cag ggc ggc gag gcc ccc aga gag gtg acc agc 144
Gly Val Arg Pro Ser Gln Gly Gly Glu Ala Pro Arg Glu Val Thr Ser
35 40 45
gac agc ggc agc gtg gtg agc ggc ctg acc ccc ggc gtg gag tac gtg 192
Asp Ser Gly Ser Val Val Ser Gly Leu Thr Pro Gly Val Glu Tyr Val
50 55 60
tac acc atc cag gtg ctg aga gac ggc cag gag aga gac gcc ccc atc 240
Tyr Thr Ile Gln Val Leu Arg Asp Gly Gln Glu Arg Asp Ala Pro Ile
65 70 75 80
gtg aac aag gtg gtg acc 258
Val Asn Lys Val Val Thr
85
<210> 40
<211> 86
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 40
Gln Pro Gly Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val Thr Glu Thr
1 5 10 15
Thr Ile Val Ile Thr Trp Thr Pro Ala Pro Arg Leu Gly Phe Lys Leu
20 25 30
Gly Val Arg Pro Ser Gln Gly Gly Glu Ala Pro Arg Glu Val Thr Ser
35 40 45
Asp Ser Gly Ser Val Val Ser Gly Leu Thr Pro Gly Val Glu Tyr Val
50 55 60
Tyr Thr Ile Gln Val Leu Arg Asp Gly Gln Glu Arg Asp Ala Pro Ile
65 70 75 80
Val Asn Lys Val Val Thr
85
<210> 41
<211> 282
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (7Fn3)
<220>
<221> CDS
<222> (1)..(282)
<400> 41
ccc ctg agc ccc ccc acc aac ctg cac ctg gag gcc aac ccc gac acc 48
Pro Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala Asn Pro Asp Thr
1 5 10 15
ggc gtg ctg acc gtg agc tgg gag aga agc acc acc ccc gac atc acc 96
Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr Pro Asp Ile Thr
20 25 30
ggc tac aga atc acc acc acc ccc acc aac ggc cag cag ggc aac agc 144
Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln Gln Gly Asn Ser
35 40 45
ctg gag gag gtg gtg cac gcc gac cag agc agc tgc acc ttc gac aac 192
Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys Thr Phe Asp Asn
50 55 60
ctg agc ccc ggc ctg gag tac aac gtg agc gtg tac acc gtg aag gac 240
Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr Thr Val Lys Asp
65 70 75 80
gac aag gag agc gtg ccc atc agc gac acc atc atc ccc tga 282
Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile Ile Pro
85 90
<210> 42
<211> 93
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 42
Pro Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala Asn Pro Asp Thr
1 5 10 15
Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr Pro Asp Ile Thr
20 25 30
Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln Gln Gly Asn Ser
35 40 45
Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys Thr Phe Asp Asn
50 55 60
Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr Thr Val Lys Asp
65 70 75 80
Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile Ile Pro
85 90
<210> 43
<211> 276
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (8Fn3)
<220>
<221> CDS
<222> (1)..(276)
<400> 43
gcc gtg ccc ccc ccc acc gac ctg aga ttc acc aac atc ggc ccc gac 48
Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn Ile Gly Pro Asp
1 5 10 15
acc atg aga gtg acc tgg gcc ccc ccc ccc agc atc gac ctg acc aac 96
Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser Ile Asp Leu Thr Asn
20 25 30
ttc ctg gtg aga tac agc ccc gtg aag aac gag gag gac gtg gcc gag 144
Phe Leu Val Arg Tyr Ser Pro Val Lys Asn Glu Glu Asp Val Ala Glu
35 40 45
ctg agc atc agc ccc agc gac aac gcc gtg gtg ctg acc aac ctg ctg 192
Leu Ser Ile Ser Pro Ser Asp Asn Ala Val Val Leu Thr Asn Leu Leu
50 55 60
ccc ggc acc gag tac gtg gtg agc gtg agc agc gtg tac gag cag cac 240
Pro Gly Thr Glu Tyr Val Val Ser Val Ser Ser Val Tyr Glu Gln His
65 70 75 80
gag agc acc ccc ctg aga ggc aga cag aag acc tga 276
Glu Ser Thr Pro Leu Arg Gly Arg Gln Lys Thr
85 90
<210> 44
<211> 91
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 44
Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn Ile Gly Pro Asp
1 5 10 15
Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser Ile Asp Leu Thr Asn
20 25 30
Phe Leu Val Arg Tyr Ser Pro Val Lys Asn Glu Glu Asp Val Ala Glu
35 40 45
Leu Ser Ile Ser Pro Ser Asp Asn Ala Val Val Leu Thr Asn Leu Leu
50 55 60
Pro Gly Thr Glu Tyr Val Val Ser Val Ser Ser Val Tyr Glu Gln His
65 70 75 80
Glu Ser Thr Pro Leu Arg Gly Arg Gln Lys Thr
85 90
<210> 45
<211> 273
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (9Fn3)
<220>
<221> CDS
<222> (1)..(273)
<400> 45
ggc ctg gac agc ccc acc ggc atc gac ttc agc gac atc acc gcc aac 48
Gly Leu Asp Ser Pro Thr Gly Ile Asp Phe Ser Asp Ile Thr Ala Asn
1 5 10 15
agc ttc acc gtg cac tgg atc gcc ccc aga gcc acc atc acc ggc tac 96
Ser Phe Thr Val His Trp Ile Ala Pro Arg Ala Thr Ile Thr Gly Tyr
20 25 30
aga atc aga cac cac ccc gag cac ttc agc ggc aga ccc aga gag gac 144
Arg Ile Arg His His Pro Glu His Phe Ser Gly Arg Pro Arg Glu Asp
35 40 45
aga gtg ccc cac agc aga aac agc atc acc ctg acc aac ctg acc ccc 192
Arg Val Pro His Ser Arg Asn Ser Ile Thr Leu Thr Asn Leu Thr Pro
50 55 60
ggc acc gag tac gtg gtg agc atc gtg gcc ctg aac ggc aga gag gag 240
Gly Thr Glu Tyr Val Val Ser Ile Val Ala Leu Asn Gly Arg Glu Glu
65 70 75 80
agc ccc ctg ctg atc ggc cag cag agc acc tga 273
Ser Pro Leu Leu Ile Gly Gln Gln Ser Thr
85 90
<210> 46
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 46
Gly Leu Asp Ser Pro Thr Gly Ile Asp Phe Ser Asp Ile Thr Ala Asn
1 5 10 15
Ser Phe Thr Val His Trp Ile Ala Pro Arg Ala Thr Ile Thr Gly Tyr
20 25 30
Arg Ile Arg His His Pro Glu His Phe Ser Gly Arg Pro Arg Glu Asp
35 40 45
Arg Val Pro His Ser Arg Asn Ser Ile Thr Leu Thr Asn Leu Thr Pro
50 55 60
Gly Thr Glu Tyr Val Val Ser Ile Val Ala Leu Asn Gly Arg Glu Glu
65 70 75 80
Ser Pro Leu Leu Ile Gly Gln Gln Ser Thr
85 90
<210> 47
<211> 279
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (10Fn3)
<220>
<221> CDS
<222> (1)..(279)
<400> 47
gtg agc gac gtg ccc aga gac ctg gtg gtg gcc gcc acc ccc acc agc 48
Val Ser Asp Val Pro Arg Asp Leu Val Val Ala Ala Thr Pro Thr Ser
1 5 10 15
ctg ctg atc agc tgg gac gcc ccc gcc gtg acc gtg aga tac tac aga 96
Leu Leu Ile Ser Trp Asp Ala Pro Ala Val Thr Val Arg Tyr Tyr Arg
20 25 30
atc acc tac ggc gag acc ggc ggc aac agc ccc gtg cag gag ttc acc 144
Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe Thr
35 40 45
gtg ccc ggc agc aag agc acc gcc acc atc agc ggc ctg aag ccc ggc 192
Val Pro Gly Ser Lys Ser Thr Ala Thr Ile Ser Gly Leu Lys Pro Gly
50 55 60
gtg gac tac acc atc acc gtg tac gcc gtg acc ggc aga ggc gac agc 240
Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Gly Arg Gly Asp Ser
65 70 75 80
ccc gcc agc agc aag ccc atc agc atc aac tac aga acc 279
Pro Ala Ser Ser Lys Pro Ile Ser Ile Asn Tyr Arg Thr
85 90
<210> 48
<211> 93
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 48
Val Ser Asp Val Pro Arg Asp Leu Val Val Ala Ala Thr Pro Thr Ser
1 5 10 15
Leu Leu Ile Ser Trp Asp Ala Pro Ala Val Thr Val Arg Tyr Tyr Arg
20 25 30
Ile Thr Tyr Gly Glu Thr Gly Gly Asn Ser Pro Val Gln Glu Phe Thr
35 40 45
Val Pro Gly Ser Lys Ser Thr Ala Thr Ile Ser Gly Leu Lys Pro Gly
50 55 60
Val Asp Tyr Thr Ile Thr Val Tyr Ala Val Thr Gly Arg Gly Asp Ser
65 70 75 80
Pro Ala Ser Ser Lys Pro Ile Ser Ile Asn Tyr Arg Thr
85 90
<210> 49
<211> 270
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (11Fn3)
<220>
<221> CDS
<222> (1)..(270)
<400> 49
gag atc gac aag ccc agc cag atg cag gtg acc gac gtg cag gac aac 48
Glu Ile Asp Lys Pro Ser Gln Met Gln Val Thr Asp Val Gln Asp Asn
1 5 10 15
agc atc agc gtg aag tgg ctg ccc agc agc agc ccc gtg acc ggc tac 96
Ser Ile Ser Val Lys Trp Leu Pro Ser Ser Ser Pro Val Thr Gly Tyr
20 25 30
aga gtg acc acc acc ccc aag aac ggc ccc ggc ccc acc aag acc aag 144
Arg Val Thr Thr Thr Pro Lys Asn Gly Pro Gly Pro Thr Lys Thr Lys
35 40 45
acc gcc ggc ccc gac cag acc gag atg acc atc gag ggc ctg cag ccc 192
Thr Ala Gly Pro Asp Gln Thr Glu Met Thr Ile Glu Gly Leu Gln Pro
50 55 60
acc gtg gag tac gtg gtg agc gtg tac gcc cag aac ccc agc ggc gag 240
Thr Val Glu Tyr Val Val Ser Val Tyr Ala Gln Asn Pro Ser Gly Glu
65 70 75 80
agc cag ccc ctg gtg cag acc gcc gtg acc 270
Ser Gln Pro Leu Val Gln Thr Ala Val Thr
85 90
<210> 50
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 50
Glu Ile Asp Lys Pro Ser Gln Met Gln Val Thr Asp Val Gln Asp Asn
1 5 10 15
Ser Ile Ser Val Lys Trp Leu Pro Ser Ser Ser Pro Val Thr Gly Tyr
20 25 30
Arg Val Thr Thr Thr Pro Lys Asn Gly Pro Gly Pro Thr Lys Thr Lys
35 40 45
Thr Ala Gly Pro Asp Gln Thr Glu Met Thr Ile Glu Gly Leu Gln Pro
50 55 60
Thr Val Glu Tyr Val Val Ser Val Tyr Ala Gln Asn Pro Ser Gly Glu
65 70 75 80
Ser Gln Pro Leu Val Gln Thr Ala Val Thr
85 90
<210> 51
<211> 273
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (12Fn3)
<220>
<221> CDS
<222> (1)..(273)
<400> 51
aac atc gac aga ccc aag ggc ctg gcc ttc acc gac gtg gac gtg gac 48
Asn Ile Asp Arg Pro Lys Gly Leu Ala Phe Thr Asp Val Asp Val Asp
1 5 10 15
agc atc aag atc gcc tgg gag agc ccc cag ggc cag gtg agc aga tac 96
Ser Ile Lys Ile Ala Trp Glu Ser Pro Gln Gly Gln Val Ser Arg Tyr
20 25 30
aga gtg acc tac agc agc ccc gag gac ggc atc cac gag ctg ttc ccc 144
Arg Val Thr Tyr Ser Ser Pro Glu Asp Gly Ile His Glu Leu Phe Pro
35 40 45
gcc ccc gac ggc gag gag gac acc gcc gag ctg cag ggc ctg aga ccc 192
Ala Pro Asp Gly Glu Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro
50 55 60
ggc agc gag tac acc gtg agc gtg gtg gcc ctg cac gac gac atg gag 240
Gly Ser Glu Tyr Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu
65 70 75 80
agc cag ccc ctg atc ggc acc cag agc acc tga 273
Ser Gln Pro Leu Ile Gly Thr Gln Ser Thr
85 90
<210> 52
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 52
Asn Ile Asp Arg Pro Lys Gly Leu Ala Phe Thr Asp Val Asp Val Asp
1 5 10 15
Ser Ile Lys Ile Ala Trp Glu Ser Pro Gln Gly Gln Val Ser Arg Tyr
20 25 30
Arg Val Thr Tyr Ser Ser Pro Glu Asp Gly Ile His Glu Leu Phe Pro
35 40 45
Ala Pro Asp Gly Glu Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro
50 55 60
Gly Ser Glu Tyr Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu
65 70 75 80
Ser Gln Pro Leu Ile Gly Thr Gln Ser Thr
85 90
<210> 53
<211> 276
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (13Fn3)
<220>
<221> CDS
<222> (1)..(276)
<400> 53
gcc atc ccc gcc ccc acc gac ctg aag ttc acc cag gtg acc ccc acc 48
Ala Ile Pro Ala Pro Thr Asp Leu Lys Phe Thr Gln Val Thr Pro Thr
1 5 10 15
agc ctg agc gcc cag tgg acc ccc ccc aac gtg cag ctg acc ggc tac 96
Ser Leu Ser Ala Gln Trp Thr Pro Pro Asn Val Gln Leu Thr Gly Tyr
20 25 30
aga gtg aga gtg acc ccc aag gag aag acc ggc ccc atg aag gag atc 144
Arg Val Arg Val Thr Pro Lys Glu Lys Thr Gly Pro Met Lys Glu Ile
35 40 45
aac ctg gcc ccc gac agc agc agc gtg gtg gtg agc ggc ctg atg gtg 192
Asn Leu Ala Pro Asp Ser Ser Ser Val Val Val Ser Gly Leu Met Val
50 55 60
gcc acc aag tac gag gtg agc gtg tac gcc ctg aag gac acc ctg acc 240
Ala Thr Lys Tyr Glu Val Ser Val Tyr Ala Leu Lys Asp Thr Leu Thr
65 70 75 80
agc aga ccc gcc cag ggc gtg gtg acc acc ctg gag 276
Ser Arg Pro Ala Gln Gly Val Val Thr Thr Leu Glu
85 90
<210> 54
<211> 92
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 54
Ala Ile Pro Ala Pro Thr Asp Leu Lys Phe Thr Gln Val Thr Pro Thr
1 5 10 15
Ser Leu Ser Ala Gln Trp Thr Pro Pro Asn Val Gln Leu Thr Gly Tyr
20 25 30
Arg Val Arg Val Thr Pro Lys Glu Lys Thr Gly Pro Met Lys Glu Ile
35 40 45
Asn Leu Ala Pro Asp Ser Ser Ser Val Val Val Ser Gly Leu Met Val
50 55 60
Ala Thr Lys Tyr Glu Val Ser Val Tyr Ala Leu Lys Asp Thr Leu Thr
65 70 75 80
Ser Arg Pro Ala Gln Gly Val Val Thr Thr Leu Glu
85 90
<210> 55
<211> 264
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (14Fn3)
<220>
<221> CDS
<222> (1)..(264)
<400> 55
aac gtg agc ccc ccc aga aga gcc aga gtg acc gac gcc acc gag acc 48
Asn Val Ser Pro Pro Arg Arg Ala Arg Val Thr Asp Ala Thr Glu Thr
1 5 10 15
acc atc acc atc agc tgg aga acc aag acc gag acc atc acc ggc ttc 96
Thr Ile Thr Ile Ser Trp Arg Thr Lys Thr Glu Thr Ile Thr Gly Phe
20 25 30
cag gtg gac gcc gtg ccc gcc aac ggc cag acc ccc atc cag aga acc 144
Gln Val Asp Ala Val Pro Ala Asn Gly Gln Thr Pro Ile Gln Arg Thr
35 40 45
atc aag ccc gac gtg aga agc tac acc atc acc ggc ctg cag ccc ggc 192
Ile Lys Pro Asp Val Arg Ser Tyr Thr Ile Thr Gly Leu Gln Pro Gly
50 55 60
acc gac tac aag atc tac ctg tac acc ctg aac gac aac gcc aga agc 240
Thr Asp Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp Asn Ala Arg Ser
65 70 75 80
agc gtg gtg atc gac gcc agc acc 264
Ser Val Val Ile Asp Ala Ser Thr
85
<210> 56
<211> 88
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 56
Asn Val Ser Pro Pro Arg Arg Ala Arg Val Thr Asp Ala Thr Glu Thr
1 5 10 15
Thr Ile Thr Ile Ser Trp Arg Thr Lys Thr Glu Thr Ile Thr Gly Phe
20 25 30
Gln Val Asp Ala Val Pro Ala Asn Gly Gln Thr Pro Ile Gln Arg Thr
35 40 45
Ile Lys Pro Asp Val Arg Ser Tyr Thr Ile Thr Gly Leu Gln Pro Gly
50 55 60
Thr Asp Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp Asn Ala Arg Ser
65 70 75 80
Ser Val Val Ile Asp Ala Ser Thr
85
<210> 57
<211> 270
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (15Fn3)
<220>
<221> CDS
<222> (1)..(270)
<400> 57
gcc atc gac gcc ccc agc aac ctg aga ttc ctg gcc acc acc ccc aac 48
Ala Ile Asp Ala Pro Ser Asn Leu Arg Phe Leu Ala Thr Thr Pro Asn
1 5 10 15
agc ctg ctg gtg agc tgg cag ccc ccc aga gcc aga atc acc ggc tac 96
Ser Leu Leu Val Ser Trp Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr
20 25 30
atc atc aag tac gag aag ccc ggc agc ccc ccc aga gag gtg gtg ccc 144
Ile Ile Lys Tyr Glu Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro
35 40 45
aga ccc aga ccc ggc gtg acc gag gcc acc atc acc ggc ctg gag ccc 192
Arg Pro Arg Pro Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro
50 55 60
ggc acc gag tac acc atc tac gtg atc gcc ctg aag aac aac cag aag 240
Gly Thr Glu Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys
65 70 75 80
agc gag ccc ctg atc ggc aga aag aag acc 270
Ser Glu Pro Leu Ile Gly Arg Lys Lys Thr
85 90
<210> 58
<211> 90
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 58
Ala Ile Asp Ala Pro Ser Asn Leu Arg Phe Leu Ala Thr Thr Pro Asn
1 5 10 15
Ser Leu Leu Val Ser Trp Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr
20 25 30
Ile Ile Lys Tyr Glu Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro
35 40 45
Arg Pro Arg Pro Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro
50 55 60
Gly Thr Glu Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys
65 70 75 80
Ser Glu Pro Leu Ile Gly Arg Lys Lys Thr
85 90
<210> 59
<211> 264
<212> DNA
<213> 人工序列
<220>
<223> Pronectins (16Fn3)
<220>
<221> CDS
<222> (1)..(264)
<400> 59
ccc ggc ctg aac ccc aac gcc agc acc ggc cag gag gcc ctg agc cag 48
Pro Gly Leu Asn Pro Asn Ala Ser Thr Gly Gln Glu Ala Leu Ser Gln
1 5 10 15
acc acc atc agc tgg gcc ccc ttc cag gac acc agc gag tac atc atc 96
Thr Thr Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr Ile Ile
20 25 30
agc tgc cac ccc gtg ggc acc gac gag gag ccc ctg cag ttc aga gtg 144
Ser Cys His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln Phe Arg Val
35 40 45
ccc ggc acc agc acc agc gcc acc ctg acc ggc ctg acc aga ggc gcc 192
Pro Gly Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu Thr Arg Gly Ala
50 55 60
acc tac aac atc atc gtg gag gcc ctg aag gac cag cag aga cac aag 240
Thr Tyr Asn Ile Ile Val Glu Ala Leu Lys Asp Gln Gln Arg His Lys
65 70 75 80
gtg aga gag gag gtg gtg acc gtg 264
Val Arg Glu Glu Val Val Thr Val
85
<210> 60
<211> 88
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 60
Pro Gly Leu Asn Pro Asn Ala Ser Thr Gly Gln Glu Ala Leu Ser Gln
1 5 10 15
Thr Thr Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr Ile Ile
20 25 30
Ser Cys His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln Phe Arg Val
35 40 45
Pro Gly Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu Thr Arg Gly Ala
50 55 60
Thr Tyr Asn Ile Ile Val Glu Ala Leu Lys Asp Gln Gln Arg His Lys
65 70 75 80
Val Arg Glu Glu Val Val Thr Val
85
<210> 61
<211> 276
<212> DNA
<213> 人工序列
<220>
<223> Adhiron
<220>
<221> CDS
<222> (1)..(276)
<400> 61
gcc acc ggc gtg aga gcc gtg ccc ggc aac gag aac agc ctg gag atc 48
Ala Thr Gly Val Arg Ala Val Pro Gly Asn Glu Asn Ser Leu Glu Ile
1 5 10 15
gag gag ctg gcc aga ttc gcc gtg gac gag cac aac aag aag gag aac 96
Glu Glu Leu Ala Arg Phe Ala Val Asp Glu His Asn Lys Lys Glu Asn
20 25 30
gcc ctg ctg gag ttc gtg aga gtg gtg aag gcc aag gag cag gtg gtg 144
Ala Leu Leu Glu Phe Val Arg Val Val Lys Ala Lys Glu Gln Val Val
35 40 45
gcc ggc acc atg tac tac ctg acc ctg gag gcc aag gac ggc ggc aag 192
Ala Gly Thr Met Tyr Tyr Leu Thr Leu Glu Ala Lys Asp Gly Gly Lys
50 55 60
aag aag ctg tac gag gcc aag gtg tgg gtg aag ccc tgg gag aac ttc 240
Lys Lys Leu Tyr Glu Ala Lys Val Trp Val Lys Pro Trp Glu Asn Phe
65 70 75 80
aag gag ctg cag gag ttc aag ccc gtg ggc gac gcc 276
Lys Glu Leu Gln Glu Phe Lys Pro Val Gly Asp Ala
85 90
<210> 62
<211> 92
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 62
Ala Thr Gly Val Arg Ala Val Pro Gly Asn Glu Asn Ser Leu Glu Ile
1 5 10 15
Glu Glu Leu Ala Arg Phe Ala Val Asp Glu His Asn Lys Lys Glu Asn
20 25 30
Ala Leu Leu Glu Phe Val Arg Val Val Lys Ala Lys Glu Gln Val Val
35 40 45
Ala Gly Thr Met Tyr Tyr Leu Thr Leu Glu Ala Lys Asp Gly Gly Lys
50 55 60
Lys Lys Leu Tyr Glu Ala Lys Val Trp Val Lys Pro Trp Glu Asn Phe
65 70 75 80
Lys Glu Leu Gln Glu Phe Lys Pro Val Gly Asp Ala
85 90
<210> 63
<211> 177
<212> DNA
<213> 人工序列
<220>
<223> 亲和体
<220>
<221> CDS
<222> (1)..(177)
<400> 63
gtg gac aac aag ttc aac aag gag cag cag aac gcc ttc tac gag atc 48
Val Asp Asn Lys Phe Asn Lys Glu Gln Gln Asn Ala Phe Tyr Glu Ile
1 5 10 15
ctg cac ctg ccc aac ctg aac gag gag cag aga aac gcc ttc atc cag 96
Leu His Leu Pro Asn Leu Asn Glu Glu Gln Arg Asn Ala Phe Ile Gln
20 25 30
agc ctg aag gac gac ccc agc cag agc gcc aac ctg ctg gcc gag gcc 144
Ser Leu Lys Asp Asp Pro Ser Gln Ser Ala Asn Leu Leu Ala Glu Ala
35 40 45
aag aag ctg aac gac gcc cag gcc ccc aag tga 177
Lys Lys Leu Asn Asp Ala Gln Ala Pro Lys
50 55
<210> 64
<211> 58
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 64
Val Asp Asn Lys Phe Asn Lys Glu Gln Gln Asn Ala Phe Tyr Glu Ile
1 5 10 15
Leu His Leu Pro Asn Leu Asn Glu Glu Gln Arg Asn Ala Phe Ile Gln
20 25 30
Ser Leu Lys Asp Asp Pro Ser Gln Ser Ala Asn Leu Leu Ala Glu Ala
35 40 45
Lys Lys Leu Asn Asp Ala Gln Ala Pro Lys
50 55
<210> 65
<211> 522
<212> DNA
<213> 人工序列
<220>
<223> Affilins (γ-B晶状体蛋白)
<220>
<221> CDS
<222> (1)..(522)
<400> 65
ggc aag atc acc ttc tac gag gac aga gcc ttc cag ggc aga agc tac 48
Gly Lys Ile Thr Phe Tyr Glu Asp Arg Ala Phe Gln Gly Arg Ser Tyr
1 5 10 15
gag tgc acc acc gac tgc ccc aac ctg cag ccc tac ttc agc aga tgc 96
Glu Cys Thr Thr Asp Cys Pro Asn Leu Gln Pro Tyr Phe Ser Arg Cys
20 25 30
aac agc atc aga gtg gag agc ggc tgc tgg atg atc tac gag aga ccc 144
Asn Ser Ile Arg Val Glu Ser Gly Cys Trp Met Ile Tyr Glu Arg Pro
35 40 45
aac tac cag ggc cac cag tac ttc ctg aga aga ggc gag tac ccc gac 192
Asn Tyr Gln Gly His Gln Tyr Phe Leu Arg Arg Gly Glu Tyr Pro Asp
50 55 60
tac cag cag tgg atg ggc ctg agc gac agc atc aga agc tgc tgc ctg 240
Tyr Gln Gln Trp Met Gly Leu Ser Asp Ser Ile Arg Ser Cys Cys Leu
65 70 75 80
atc ccc ccc cac agc ggc gcc tac aga atg aag atc tac gac aga gac 288
Ile Pro Pro His Ser Gly Ala Tyr Arg Met Lys Ile Tyr Asp Arg Asp
85 90 95
gag ctg aga ggc cag atg agc gag ctg acc gac gac tgc atc agc gtg 336
Glu Leu Arg Gly Gln Met Ser Glu Leu Thr Asp Asp Cys Ile Ser Val
100 105 110
cag gac aga ttc cac ctg acc gag atc cac agc ctg aac gtg ctg gag 384
Gln Asp Arg Phe His Leu Thr Glu Ile His Ser Leu Asn Val Leu Glu
115 120 125
ggc agc tgg atc ctg tac gag atg ccc aac tac aga ggc aga cag tac 432
Gly Ser Trp Ile Leu Tyr Glu Met Pro Asn Tyr Arg Gly Arg Gln Tyr
130 135 140
ctg ctg aga ccc ggc gag tac aga aga ttc ctg gac tgg ggc gcc ccc 480
Leu Leu Arg Pro Gly Glu Tyr Arg Arg Phe Leu Asp Trp Gly Ala Pro
145 150 155 160
aac gcc aag gtg ggc agc ctg aga aga gtg atg gac ctg tac 522
Asn Ala Lys Val Gly Ser Leu Arg Arg Val Met Asp Leu Tyr
165 170
<210> 66
<211> 174
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 66
Gly Lys Ile Thr Phe Tyr Glu Asp Arg Ala Phe Gln Gly Arg Ser Tyr
1 5 10 15
Glu Cys Thr Thr Asp Cys Pro Asn Leu Gln Pro Tyr Phe Ser Arg Cys
20 25 30
Asn Ser Ile Arg Val Glu Ser Gly Cys Trp Met Ile Tyr Glu Arg Pro
35 40 45
Asn Tyr Gln Gly His Gln Tyr Phe Leu Arg Arg Gly Glu Tyr Pro Asp
50 55 60
Tyr Gln Gln Trp Met Gly Leu Ser Asp Ser Ile Arg Ser Cys Cys Leu
65 70 75 80
Ile Pro Pro His Ser Gly Ala Tyr Arg Met Lys Ile Tyr Asp Arg Asp
85 90 95
Glu Leu Arg Gly Gln Met Ser Glu Leu Thr Asp Asp Cys Ile Ser Val
100 105 110
Gln Asp Arg Phe His Leu Thr Glu Ile His Ser Leu Asn Val Leu Glu
115 120 125
Gly Ser Trp Ile Leu Tyr Glu Met Pro Asn Tyr Arg Gly Arg Gln Tyr
130 135 140
Leu Leu Arg Pro Gly Glu Tyr Arg Arg Phe Leu Asp Trp Gly Ala Pro
145 150 155 160
Asn Ala Lys Val Gly Ser Leu Arg Arg Val Met Asp Leu Tyr
165 170
<210> 67
<211> 294
<212> DNA
<213> 人工序列
<220>
<223> Affimers
<220>
<221> CDS
<222> (1)..(294)
<400> 67
atg atc ccc aga ggc ctg agc gag gcc aag ccc gcc acc ccc gag atc 48
Met Ile Pro Arg Gly Leu Ser Glu Ala Lys Pro Ala Thr Pro Glu Ile
1 5 10 15
cag gag atc gtg gac aag gtg aag ccc cag ctg gag gag aag acc aac 96
Gln Glu Ile Val Asp Lys Val Lys Pro Gln Leu Glu Glu Lys Thr Asn
20 25 30
gag acc tac ggc aag ctg gag gcc gtg cag tac aag acc cag gtg ctg 144
Glu Thr Tyr Gly Lys Leu Glu Ala Val Gln Tyr Lys Thr Gln Val Leu
35 40 45
gcc agc acc aac tac tac atc aag gtg aga gcc ggc gac aac aag tac 192
Ala Ser Thr Asn Tyr Tyr Ile Lys Val Arg Ala Gly Asp Asn Lys Tyr
50 55 60
atg cac ctg aag gtg ttc aac ggc ccc ccc ggc cag aac gcc gac aga 240
Met His Leu Lys Val Phe Asn Gly Pro Pro Gly Gln Asn Ala Asp Arg
65 70 75 80
gtg ctg acc ggc tac cag gtg gac aag aac aag gac gac gag ctg acc 288
Val Leu Thr Gly Tyr Gln Val Asp Lys Asn Lys Asp Asp Glu Leu Thr
85 90 95
ggc ttc 294
Gly Phe
<210> 68
<211> 98
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 68
Met Ile Pro Arg Gly Leu Ser Glu Ala Lys Pro Ala Thr Pro Glu Ile
1 5 10 15
Gln Glu Ile Val Asp Lys Val Lys Pro Gln Leu Glu Glu Lys Thr Asn
20 25 30
Glu Thr Tyr Gly Lys Leu Glu Ala Val Gln Tyr Lys Thr Gln Val Leu
35 40 45
Ala Ser Thr Asn Tyr Tyr Ile Lys Val Arg Ala Gly Asp Asn Lys Tyr
50 55 60
Met His Leu Lys Val Phe Asn Gly Pro Pro Gly Gln Asn Ala Asp Arg
65 70 75 80
Val Leu Thr Gly Tyr Gln Val Asp Lys Asn Lys Asp Asp Glu Leu Thr
85 90 95
Gly Phe
<210> 69
<211> 462
<212> DNA
<213> 人工序列
<220>
<223> Anticalin (脂质运载蛋白Lcn1)
<220>
<221> CDS
<222> (1)..(462)
<400> 69
atc gcc agc gac gag gag atc cag gac gtg agc ggc acc tgg tac ctg 48
Ile Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu
1 5 10 15
aag gcc atg acc gtg gac aga gag ttc ccc gag atg aac ctg gag agc 96
Lys Ala Met Thr Val Asp Arg Glu Phe Pro Glu Met Asn Leu Glu Ser
20 25 30
gtg acc ccc atg acc ctg acc acc ctg gag ggc ggc aac ctg gag gcc 144
Val Thr Pro Met Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala
35 40 45
aag gtg acc atg ctg atc agc ggc aga tgc cag gag gtg aag gcc gtg 192
Lys Val Thr Met Leu Ile Ser Gly Arg Cys Gln Glu Val Lys Ala Val
50 55 60
ctg gag aag acc gac gag ccc ggc aag tac acc gcc gac ggc ggc aag 240
Leu Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Ala Asp Gly Gly Lys
65 70 75 80
cac gtg gcc tac atc atc aga agc cac gtg aag gac cac tac atc ttc 288
His Val Ala Tyr Ile Ile Arg Ser His Val Lys Asp His Tyr Ile Phe
85 90 95
tac agc gag ggc gag ctg cac ggc aag ccc gtg aga ggc gtg aag ctg 336
Tyr Ser Glu Gly Glu Leu His Gly Lys Pro Val Arg Gly Val Lys Leu
100 105 110
gtg ggc aga gac ccc aag aac aac ctg gag gcc ctg ctg gac ttc gag 384
Val Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala Leu Leu Asp Phe Glu
115 120 125
aag gcc gcc ggc gcc aga ggc ctg agc acc gag agc atc ctg atc ccc 432
Lys Ala Ala Gly Ala Arg Gly Leu Ser Thr Glu Ser Ile Leu Ile Pro
130 135 140
aga cag agc gag acc tgc agc ccc ggc agc 462
Arg Gln Ser Glu Thr Cys Ser Pro Gly Ser
145 150
<210> 70
<211> 154
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 70
Ile Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu
1 5 10 15
Lys Ala Met Thr Val Asp Arg Glu Phe Pro Glu Met Asn Leu Glu Ser
20 25 30
Val Thr Pro Met Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala
35 40 45
Lys Val Thr Met Leu Ile Ser Gly Arg Cys Gln Glu Val Lys Ala Val
50 55 60
Leu Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Ala Asp Gly Gly Lys
65 70 75 80
His Val Ala Tyr Ile Ile Arg Ser His Val Lys Asp His Tyr Ile Phe
85 90 95
Tyr Ser Glu Gly Glu Leu His Gly Lys Pro Val Arg Gly Val Lys Leu
100 105 110
Val Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala Leu Leu Asp Phe Glu
115 120 125
Lys Ala Ala Gly Ala Arg Gly Leu Ser Thr Glu Ser Ile Leu Ile Pro
130 135 140
Arg Gln Ser Glu Thr Cys Ser Pro Gly Ser
145 150
<210> 71
<211> 534
<212> DNA
<213> 人工序列
<220>
<223> Anticalins (脂质运载蛋白Lcn2)
<220>
<221> CDS
<222> (1)..(534)
<400> 71
cag gac agc acc agc gac ctg atc ccc gcc ccc ccc ctg agc aag gtg 48
Gln Asp Ser Thr Ser Asp Leu Ile Pro Ala Pro Pro Leu Ser Lys Val
1 5 10 15
ccc ctg cag cag aac ttc cag gac aac cag ttc cag ggc aag tgg tac 96
Pro Leu Gln Gln Asn Phe Gln Asp Asn Gln Phe Gln Gly Lys Trp Tyr
20 25 30
gtg gtg ggc ctg gcc ggc aac gcc atc ctg aga gag gac aag gac ccc 144
Val Val Gly Leu Ala Gly Asn Ala Ile Leu Arg Glu Asp Lys Asp Pro
35 40 45
cag aag atg tac gcc acc atc tac gag ctg aag gag gac aag agc tac 192
Gln Lys Met Tyr Ala Thr Ile Tyr Glu Leu Lys Glu Asp Lys Ser Tyr
50 55 60
aac gtg acc agc gtg ctg ttc aga aag aag aag tgc gac tac tgg atc 240
Asn Val Thr Ser Val Leu Phe Arg Lys Lys Lys Cys Asp Tyr Trp Ile
65 70 75 80
aga acc ttc gtg ccc ggc tgc cag ccc ggc gag ttc acc ctg ggc aac 288
Arg Thr Phe Val Pro Gly Cys Gln Pro Gly Glu Phe Thr Leu Gly Asn
85 90 95
atc aag agc tac ccc ggc ctg acc agc tac ctg gtg aga gtg gtg agc 336
Ile Lys Ser Tyr Pro Gly Leu Thr Ser Tyr Leu Val Arg Val Val Ser
100 105 110
acc aac tac aac cag cac gcc atg gtg ttc ttc aag aag gtg agc cag 384
Thr Asn Tyr Asn Gln His Ala Met Val Phe Phe Lys Lys Val Ser Gln
115 120 125
aac aga gag tac ttc aag atc acc ctg tac ggc aga acc aag gag ctg 432
Asn Arg Glu Tyr Phe Lys Ile Thr Leu Tyr Gly Arg Thr Lys Glu Leu
130 135 140
acc agc gag ctg aag gag aac ttc atc aga ttc agc aag agc ctg ggc 480
Thr Ser Glu Leu Lys Glu Asn Phe Ile Arg Phe Ser Lys Ser Leu Gly
145 150 155 160
ctg ccc gag aac cac atc gtg ttc ccc gtg ccc atc gac cag tgc atc 528
Leu Pro Glu Asn His Ile Val Phe Pro Val Pro Ile Asp Gln Cys Ile
165 170 175
gac ggc 534
Asp Gly
<210> 72
<211> 178
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 72
Gln Asp Ser Thr Ser Asp Leu Ile Pro Ala Pro Pro Leu Ser Lys Val
1 5 10 15
Pro Leu Gln Gln Asn Phe Gln Asp Asn Gln Phe Gln Gly Lys Trp Tyr
20 25 30
Val Val Gly Leu Ala Gly Asn Ala Ile Leu Arg Glu Asp Lys Asp Pro
35 40 45
Gln Lys Met Tyr Ala Thr Ile Tyr Glu Leu Lys Glu Asp Lys Ser Tyr
50 55 60
Asn Val Thr Ser Val Leu Phe Arg Lys Lys Lys Cys Asp Tyr Trp Ile
65 70 75 80
Arg Thr Phe Val Pro Gly Cys Gln Pro Gly Glu Phe Thr Leu Gly Asn
85 90 95
Ile Lys Ser Tyr Pro Gly Leu Thr Ser Tyr Leu Val Arg Val Val Ser
100 105 110
Thr Asn Tyr Asn Gln His Ala Met Val Phe Phe Lys Lys Val Ser Gln
115 120 125
Asn Arg Glu Tyr Phe Lys Ile Thr Leu Tyr Gly Arg Thr Lys Glu Leu
130 135 140
Thr Ser Glu Leu Lys Glu Asn Phe Ile Arg Phe Ser Lys Ser Leu Gly
145 150 155 160
Leu Pro Glu Asn His Ile Val Phe Pro Val Pro Ile Asp Gln Cys Ile
165 170 175
Asp Gly
<210> 73
<211> 255
<212> DNA
<213> 人工序列
<220>
<223> 靶向c-MET的Avimers (C426)
<220>
<221> CDS
<222> (1)..(255)
<400> 73
tgc gag agc ggc gag ttc cag tgc cac agc acc ggc aga tgc atc ccc 48
Cys Glu Ser Gly Glu Phe Gln Cys His Ser Thr Gly Arg Cys Ile Pro
1 5 10 15
cag gag tgg gtg tgc gac ggc gac aac gac tgc gag gac agc agc gac 96
Gln Glu Trp Val Cys Asp Gly Asp Asn Asp Cys Glu Asp Ser Ser Asp
20 25 30
gag gcc ccc gac ctg tgc gcc agc gcc gag ccc acc tgc ccc agc ggc 144
Glu Ala Pro Asp Leu Cys Ala Ser Ala Glu Pro Thr Cys Pro Ser Gly
35 40 45
gag ttc cag tgc aga agc acc aac aga tgc atc ccc gag acc tgg ctg 192
Glu Phe Gln Cys Arg Ser Thr Asn Arg Cys Ile Pro Glu Thr Trp Leu
50 55 60
tgc gac ggc gac aac gac tgc gag gac ggc agc gac gag gag agc tgc 240
Cys Asp Gly Asp Asn Asp Cys Glu Asp Gly Ser Asp Glu Glu Ser Cys
65 70 75 80
acc ccc ccc acc tga 255
Thr Pro Pro Thr
<210> 74
<211> 84
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 74
Cys Glu Ser Gly Glu Phe Gln Cys His Ser Thr Gly Arg Cys Ile Pro
1 5 10 15
Gln Glu Trp Val Cys Asp Gly Asp Asn Asp Cys Glu Asp Ser Ser Asp
20 25 30
Glu Ala Pro Asp Leu Cys Ala Ser Ala Glu Pro Thr Cys Pro Ser Gly
35 40 45
Glu Phe Gln Cys Arg Ser Thr Asn Arg Cys Ile Pro Glu Thr Trp Leu
50 55 60
Cys Asp Gly Asp Asn Asp Cys Glu Asp Gly Ser Asp Glu Glu Ser Cys
65 70 75 80
Thr Pro Pro Thr
<210> 75
<211> 267
<212> DNA
<213> 人工序列
<220>
<223> Centyrins (腱糖蛋白的Fn3结构域)
<220>
<221> CDS
<222> (1)..(267)
<400> 75
ctg ccc gcc ccc aag aac ctg gtg gtg agc gag gtg acc gag gac agc 48
Leu Pro Ala Pro Lys Asn Leu Val Val Ser Glu Val Thr Glu Asp Ser
1 5 10 15
gcc aga ctg agc tgg acc gcc ccc gac gcc gcc ttc gac agc ttc ctg 96
Ala Arg Leu Ser Trp Thr Ala Pro Asp Ala Ala Phe Asp Ser Phe Leu
20 25 30
atc ggc tac ggc gag agc gag aag gtg ggc gag gcc atc gtg ctg acc 144
Ile Gly Tyr Gly Glu Ser Glu Lys Val Gly Glu Ala Ile Val Leu Thr
35 40 45
gtg ccc ggc agc gag aga agc tac gac ctg acc ggc ctg aag ccc ggc 192
Val Pro Gly Ser Glu Arg Ser Tyr Asp Leu Thr Gly Leu Lys Pro Gly
50 55 60
acc gag tac acc gtg agc atc tac ggc gtg aag ggc ggc cac aga agc 240
Thr Glu Tyr Thr Val Ser Ile Tyr Gly Val Lys Gly Gly His Arg Ser
65 70 75 80
aac ccc ctg agc gcc atc ttc acc acc 267
Asn Pro Leu Ser Ala Ile Phe Thr Thr
85
<210> 76
<211> 89
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 76
Leu Pro Ala Pro Lys Asn Leu Val Val Ser Glu Val Thr Glu Asp Ser
1 5 10 15
Ala Arg Leu Ser Trp Thr Ala Pro Asp Ala Ala Phe Asp Ser Phe Leu
20 25 30
Ile Gly Tyr Gly Glu Ser Glu Lys Val Gly Glu Ala Ile Val Leu Thr
35 40 45
Val Pro Gly Ser Glu Arg Ser Tyr Asp Leu Thr Gly Leu Lys Pro Gly
50 55 60
Thr Glu Tyr Thr Val Ser Ile Tyr Gly Val Lys Gly Gly His Arg Ser
65 70 75 80
Asn Pro Leu Ser Ala Ile Phe Thr Thr
85
<210> 77
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> Kunitz结构域/BPTI
<220>
<221> CDS
<222> (1)..(171)
<400> 77
gtg aga gag gtg tgc agc gag cag gcc gag acc ggc ccc tgc aga gcc 48
Val Arg Glu Val Cys Ser Glu Gln Ala Glu Thr Gly Pro Cys Arg Ala
1 5 10 15
atg atc agc aga tgg tac ttc gac gtg acc gag ggc aag tgc gcc ccc 96
Met Ile Ser Arg Trp Tyr Phe Asp Val Thr Glu Gly Lys Cys Ala Pro
20 25 30
ttc ttc tac ggc ggc tgc tgc ggc ggc aac aga aac aac ttc gac acc 144
Phe Phe Tyr Gly Gly Cys Cys Gly Gly Asn Arg Asn Asn Phe Asp Thr
35 40 45
gag gag tac tgc atg gcc gtg tgc ggc 171
Glu Glu Tyr Cys Met Ala Val Cys Gly
50 55
<210> 78
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 78
Val Arg Glu Val Cys Ser Glu Gln Ala Glu Thr Gly Pro Cys Arg Ala
1 5 10 15
Met Ile Ser Arg Trp Tyr Phe Asp Val Thr Glu Gly Lys Cys Ala Pro
20 25 30
Phe Phe Tyr Gly Gly Cys Cys Gly Gly Asn Arg Asn Asn Phe Asp Thr
35 40 45
Glu Glu Tyr Cys Met Ala Val Cys Gly
50 55
<210> 79
<211> 516
<212> DNA
<213> 人工序列
<220>
<223> Obodies (人AspRS)
<220>
<221> CDS
<222> (1)..(516)
<400> 79
gag atc atg gac gcc gcc gag gac tac gcc aag gag aga tac ggc atc 48
Glu Ile Met Asp Ala Ala Glu Asp Tyr Ala Lys Glu Arg Tyr Gly Ile
1 5 10 15
agc agc atg atc cag agc cag gag aag ccc gac aga gtg ctg gtg aga 96
Ser Ser Met Ile Gln Ser Gln Glu Lys Pro Asp Arg Val Leu Val Arg
20 25 30
gtg aga gac ctg acc atc cag aag gcc gac gag gtg gtg tgg gtg aga 144
Val Arg Asp Leu Thr Ile Gln Lys Ala Asp Glu Val Val Trp Val Arg
35 40 45
gcc aga gtg cac acc agc aga gcc aag ggc aag cag tgc ttc ctg gtg 192
Ala Arg Val His Thr Ser Arg Ala Lys Gly Lys Gln Cys Phe Leu Val
50 55 60
ctg aga cag cag cag ttc aac gtg cag gcc ctg gtg gcc gtg ggc gac 240
Leu Arg Gln Gln Gln Phe Asn Val Gln Ala Leu Val Ala Val Gly Asp
65 70 75 80
cac gcc agc aag cag atg gtg aag ttc gcc gcc aac atc aac aag gag 288
His Ala Ser Lys Gln Met Val Lys Phe Ala Ala Asn Ile Asn Lys Glu
85 90 95
agc atc gtg gac gtg gag ggc gtg gtg aga aag gtg aac cag aag atc 336
Ser Ile Val Asp Val Glu Gly Val Val Arg Lys Val Asn Gln Lys Ile
100 105 110
ggc agc tgc acc cag cag gac gtg gag ctg cac gtg cag aag atc tac 384
Gly Ser Cys Thr Gln Gln Asp Val Glu Leu His Val Gln Lys Ile Tyr
115 120 125
gtg atc agc ctg gcc gag ccc aga ctg ccc ctg cag ctg gac gac gcc 432
Val Ile Ser Leu Ala Glu Pro Arg Leu Pro Leu Gln Leu Asp Asp Ala
130 135 140
gtg aga ccc gag gcc gag ggc gag gag gag ggc aga gcc acc gtg aac 480
Val Arg Pro Glu Ala Glu Gly Glu Glu Glu Gly Arg Ala Thr Val Asn
145 150 155 160
cag gac acc aga ctg gac aac aga gtg atc gac ctg 516
Gln Asp Thr Arg Leu Asp Asn Arg Val Ile Asp Leu
165 170
<210> 80
<211> 172
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 80
Glu Ile Met Asp Ala Ala Glu Asp Tyr Ala Lys Glu Arg Tyr Gly Ile
1 5 10 15
Ser Ser Met Ile Gln Ser Gln Glu Lys Pro Asp Arg Val Leu Val Arg
20 25 30
Val Arg Asp Leu Thr Ile Gln Lys Ala Asp Glu Val Val Trp Val Arg
35 40 45
Ala Arg Val His Thr Ser Arg Ala Lys Gly Lys Gln Cys Phe Leu Val
50 55 60
Leu Arg Gln Gln Gln Phe Asn Val Gln Ala Leu Val Ala Val Gly Asp
65 70 75 80
His Ala Ser Lys Gln Met Val Lys Phe Ala Ala Asn Ile Asn Lys Glu
85 90 95
Ser Ile Val Asp Val Glu Gly Val Val Arg Lys Val Asn Gln Lys Ile
100 105 110
Gly Ser Cys Thr Gln Gln Asp Val Glu Leu His Val Gln Lys Ile Tyr
115 120 125
Val Ile Ser Leu Ala Glu Pro Arg Leu Pro Leu Gln Leu Asp Asp Ala
130 135 140
Val Arg Pro Glu Ala Glu Gly Glu Glu Glu Gly Arg Ala Thr Val Asn
145 150 155 160
Gln Asp Thr Arg Leu Asp Asn Arg Val Ile Asp Leu
165 170
<210> 81
<211> 267
<212> DNA
<213> 人工序列
<220>
<223> Tn3A
<220>
<221> CDS
<222> (1)..(267)
<400> 81
gcc atc gag gtg aag gac gtg acc gac acc acc gcc ctg atc acc tgg 48
Ala Ile Glu Val Lys Asp Val Thr Asp Thr Thr Ala Leu Ile Thr Trp
1 5 10 15
agc gac gag ttc ggc cac gac tac gac ggc tgc gag ctg acc tac ggc 96
Ser Asp Glu Phe Gly His Asp Tyr Asp Gly Cys Glu Leu Thr Tyr Gly
20 25 30
atc aag gac gtg ccc ggc gac aga acc acc atc gac ctg tgg tgg cac 144
Ile Lys Asp Val Pro Gly Asp Arg Thr Thr Ile Asp Leu Trp Trp His
35 40 45
agc gcc tgg tac agc atc ggc aac ctg aag ccc gac acc gag gac gtg 192
Ser Ala Trp Tyr Ser Ile Gly Asn Leu Lys Pro Asp Thr Glu Asp Val
50 55 60
agc ctg atc tgc tac acc gac cag gag gcc ggc aac ccc gcc aag gag 240
Ser Leu Ile Cys Tyr Thr Asp Gln Glu Ala Gly Asn Pro Ala Lys Glu
65 70 75 80
acc ttc acc acc ggc ctg gtg ccc aga 267
Thr Phe Thr Thr Gly Leu Val Pro Arg
85
<210> 82
<211> 89
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 82
Ala Ile Glu Val Lys Asp Val Thr Asp Thr Thr Ala Leu Ile Thr Trp
1 5 10 15
Ser Asp Glu Phe Gly His Asp Tyr Asp Gly Cys Glu Leu Thr Tyr Gly
20 25 30
Ile Lys Asp Val Pro Gly Asp Arg Thr Thr Ile Asp Leu Trp Trp His
35 40 45
Ser Ala Trp Tyr Ser Ile Gly Asn Leu Lys Pro Asp Thr Glu Asp Val
50 55 60
Ser Leu Ile Cys Tyr Thr Asp Gln Glu Ala Gly Asn Pro Ala Lys Glu
65 70 75 80
Thr Phe Thr Thr Gly Leu Val Pro Arg
85
<210> 83
<211> 276
<212> DNA
<213> 人工序列
<220>
<223> Tn3B
<220>
<221> CDS
<222> (1)..(276)
<400> 83
gcc atc gag gtg gag gac gtg acc gac acc acc gcc ctg atc acc tgg 48
Ala Ile Glu Val Glu Asp Val Thr Asp Thr Thr Ala Leu Ile Thr Trp
1 5 10 15
acc aac aga agc agc tac agc aac ctg cac ggc tgc gag ctg gcc tac 96
Thr Asn Arg Ser Ser Tyr Ser Asn Leu His Gly Cys Glu Leu Ala Tyr
20 25 30
ggc atc aag gac gtg ccc ggc gac aga acc acc atc gac ctg aac cag 144
Gly Ile Lys Asp Val Pro Gly Asp Arg Thr Thr Ile Asp Leu Asn Gln
35 40 45
ccc tac gtg cac tac agc atc ggc aac ctg aag ccc gac acc gag tac 192
Pro Tyr Val His Tyr Ser Ile Gly Asn Leu Lys Pro Asp Thr Glu Tyr
50 55 60
gag gtg agc ctg atc tgc ctg acc acc gac ggc acc tac aac aac ccc 240
Glu Val Ser Leu Ile Cys Leu Thr Thr Asp Gly Thr Tyr Asn Asn Pro
65 70 75 80
gcc aag gag acc ttc acc acc ggc ctg gtg ccc aga 276
Ala Lys Glu Thr Phe Thr Thr Gly Leu Val Pro Arg
85 90
<210> 84
<211> 92
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 84
Ala Ile Glu Val Glu Asp Val Thr Asp Thr Thr Ala Leu Ile Thr Trp
1 5 10 15
Thr Asn Arg Ser Ser Tyr Ser Asn Leu His Gly Cys Glu Leu Ala Tyr
20 25 30
Gly Ile Lys Asp Val Pro Gly Asp Arg Thr Thr Ile Asp Leu Asn Gln
35 40 45
Pro Tyr Val His Tyr Ser Ile Gly Asn Leu Lys Pro Asp Thr Glu Tyr
50 55 60
Glu Val Ser Leu Ile Cys Leu Thr Thr Asp Gly Thr Tyr Asn Asn Pro
65 70 75 80
Ala Lys Glu Thr Phe Thr Thr Gly Leu Val Pro Arg
85 90
<210> 85
<211> 177
<212> DNA
<213> 人工序列
<220>
<223> Hckomers
<220>
<221> CDS
<222> (1)..(177)
<400> 85
acc ctg ttc gtg gcc ctg tac gac tac gag gcc aga acc gag gac gag 48
Thr Leu Phe Val Ala Leu Tyr Asp Tyr Glu Ala Arg Thr Glu Asp Glu
1 5 10 15
ctg agc ttc cac aag ggc gag aag ttc cag atc ctg aac agc agc gag 96
Leu Ser Phe His Lys Gly Glu Lys Phe Gln Ile Leu Asn Ser Ser Glu
20 25 30
ggc gac tgg tgg gag gcc aga gac agc ctg acc acc ggc gag acc ggc 144
Gly Asp Trp Trp Glu Ala Arg Asp Ser Leu Thr Thr Gly Glu Thr Gly
35 40 45
tac atc ccc agc aac tac gtg gcc ccc gtg gac 177
Tyr Ile Pro Ser Asn Tyr Val Ala Pro Val Asp
50 55
<210> 86
<211> 59
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 86
Thr Leu Phe Val Ala Leu Tyr Asp Tyr Glu Ala Arg Thr Glu Asp Glu
1 5 10 15
Leu Ser Phe His Lys Gly Glu Lys Phe Gln Ile Leu Asn Ser Ser Glu
20 25 30
Gly Asp Trp Trp Glu Ala Arg Asp Ser Leu Thr Thr Gly Glu Thr Gly
35 40 45
Tyr Ile Pro Ser Asn Tyr Val Ala Pro Val Asp
50 55
<210> 87
<211> 174
<212> DNA
<213> 人工序列
<220>
<223> NPHP1
<220>
<221> CDS
<222> (1)..(174)
<400> 87
gag gag tac atc gcc gtg ggc gac ttc gac acc gcc cag cag gtg ggc 48
Glu Glu Tyr Ile Ala Val Gly Asp Phe Asp Thr Ala Gln Gln Val Gly
1 5 10 15
gac ctg acc ttc aag aag ggc gag atc ctg ctg gtg atc gag aag aag 96
Asp Leu Thr Phe Lys Lys Gly Glu Ile Leu Leu Val Ile Glu Lys Lys
20 25 30
ccc gac ggc tgg tgg atc gcc aag gac gcc aag ggc aac gag ggc ctg 144
Pro Asp Gly Trp Trp Ile Ala Lys Asp Ala Lys Gly Asn Glu Gly Leu
35 40 45
gtg ccc aga acc tac ctg gag ccc tac agc 174
Val Pro Arg Thr Tyr Leu Glu Pro Tyr Ser
50 55
<210> 88
<211> 58
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 88
Glu Glu Tyr Ile Ala Val Gly Asp Phe Asp Thr Ala Gln Gln Val Gly
1 5 10 15
Asp Leu Thr Phe Lys Lys Gly Glu Ile Leu Leu Val Ile Glu Lys Lys
20 25 30
Pro Asp Gly Trp Trp Ile Ala Lys Asp Ala Lys Gly Asn Glu Gly Leu
35 40 45
Val Pro Arg Thr Tyr Leu Glu Pro Tyr Ser
50 55
<210> 89
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> Tec
<220>
<221> CDS
<222> (1)..(171)
<400> 89
gag atc gtg gtg gcc atg tac gac ttc cag gcc gcc gag ggc cac gac 48
Glu Ile Val Val Ala Met Tyr Asp Phe Gln Ala Ala Glu Gly His Asp
1 5 10 15
ctg aga ctg gag aga cag gag tac ctg atc ctg gag aag aac gac gtg 96
Leu Arg Leu Glu Arg Gln Glu Tyr Leu Ile Leu Glu Lys Asn Asp Val
20 25 30
cac tgg tgg aga gcc aga gac aag tac ggc aac gag ggc tac atc ccc 144
His Trp Trp Arg Ala Arg Asp Lys Tyr Gly Asn Glu Gly Tyr Ile Pro
35 40 45
agc aac tac gtg acc ggc aag aag tga 171
Ser Asn Tyr Val Thr Gly Lys Lys
50 55
<210> 90
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 90
Glu Ile Val Val Ala Met Tyr Asp Phe Gln Ala Ala Glu Gly His Asp
1 5 10 15
Leu Arg Leu Glu Arg Gln Glu Tyr Leu Ile Leu Glu Lys Asn Asp Val
20 25 30
His Trp Trp Arg Ala Arg Asp Lys Tyr Gly Asn Glu Gly Tyr Ile Pro
35 40 45
Ser Asn Tyr Val Thr Gly Lys Lys
50 55
<210> 91
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> Hck
<220>
<221> CDS
<222> (1)..(171)
<400> 91
atc atc gtg gtg gcc ctg tac gac tac gag gcc atc cac cac gag gac 48
Ile Ile Val Val Ala Leu Tyr Asp Tyr Glu Ala Ile His His Glu Asp
1 5 10 15
ctg agc ttc cag aag ggc gac cag atg gtg gtg ctg gag gag agc ggc 96
Leu Ser Phe Gln Lys Gly Asp Gln Met Val Val Leu Glu Glu Ser Gly
20 25 30
gag tgg tgg aag gcc aga agc ctg gcc acc aga aag gag ggc tac atc 144
Glu Trp Trp Lys Ala Arg Ser Leu Ala Thr Arg Lys Glu Gly Tyr Ile
35 40 45
ccc agc aac tac gtg gcc aga gtg gac 171
Pro Ser Asn Tyr Val Ala Arg Val Asp
50 55
<210> 92
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 92
Ile Ile Val Val Ala Leu Tyr Asp Tyr Glu Ala Ile His His Glu Asp
1 5 10 15
Leu Ser Phe Gln Lys Gly Asp Gln Met Val Val Leu Glu Glu Ser Gly
20 25 30
Glu Trp Trp Lys Ala Arg Ser Leu Ala Thr Arg Lys Glu Gly Tyr Ile
35 40 45
Pro Ser Asn Tyr Val Ala Arg Val Asp
50 55
<210> 93
<211> 213
<212> DNA
<213> 人工序列
<220>
<223> Amph
<220>
<221> CDS
<222> (1)..(213)
<400> 93
tac aag gtg gag acc ctg cac gac ttc gag gcc gcc aac agc gac gag 48
Tyr Lys Val Glu Thr Leu His Asp Phe Glu Ala Ala Asn Ser Asp Glu
1 5 10 15
ctg acc ctg cag aga ggc gac gtg gtg ctg gtg gtg ccc agc gac agc 96
Leu Thr Leu Gln Arg Gly Asp Val Val Leu Val Val Pro Ser Asp Ser
20 25 30
gag gcc gac cag gac gcc ggc tgg ctg gtg ggc gtg aag gag agc gac 144
Glu Ala Asp Gln Asp Ala Gly Trp Leu Val Gly Val Lys Glu Ser Asp
35 40 45
tgg ctg cag tac aga gac ctg gcc acc tac aag ggc ctg ttc ccc gag 192
Trp Leu Gln Tyr Arg Asp Leu Ala Thr Tyr Lys Gly Leu Phe Pro Glu
50 55 60
aac ttc acc aga aga ctg gac 213
Asn Phe Thr Arg Arg Leu Asp
65 70
<210> 94
<211> 71
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 94
Tyr Lys Val Glu Thr Leu His Asp Phe Glu Ala Ala Asn Ser Asp Glu
1 5 10 15
Leu Thr Leu Gln Arg Gly Asp Val Val Leu Val Val Pro Ser Asp Ser
20 25 30
Glu Ala Asp Gln Asp Ala Gly Trp Leu Val Gly Val Lys Glu Ser Asp
35 40 45
Trp Leu Gln Tyr Arg Asp Leu Ala Thr Tyr Lys Gly Leu Phe Pro Glu
50 55 60
Asn Phe Thr Arg Arg Leu Asp
65 70
<210> 95
<211> 192
<212> DNA
<213> 人工序列
<220>
<223> RIMBP#3
<220>
<221> CDS
<222> (1)..(192)
<400> 95
aag atc atg atc gcc gcc ctg gac tac gac ccc ggc gac ggc cag atg 48
Lys Ile Met Ile Ala Ala Leu Asp Tyr Asp Pro Gly Asp Gly Gln Met
1 5 10 15
ggc ggc cag ggc aag ggc aga ctg gcc ctg aga gcc ggc gac gtg gtg 96
Gly Gly Gln Gly Lys Gly Arg Leu Ala Leu Arg Ala Gly Asp Val Val
20 25 30
atg gtg tac ggc ccc atg gac gac cag ggc ttc tac tac ggc gag ctg 144
Met Val Tyr Gly Pro Met Asp Asp Gln Gly Phe Tyr Tyr Gly Glu Leu
35 40 45
ggc ggc cac aga ggc ctg gtg ccc gcc cac ctg ctg gac cac atg agc 192
Gly Gly His Arg Gly Leu Val Pro Ala His Leu Leu Asp His Met Ser
50 55 60
<210> 96
<211> 64
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 96
Lys Ile Met Ile Ala Ala Leu Asp Tyr Asp Pro Gly Asp Gly Gln Met
1 5 10 15
Gly Gly Gln Gly Lys Gly Arg Leu Ala Leu Arg Ala Gly Asp Val Val
20 25 30
Met Val Tyr Gly Pro Met Asp Asp Gln Gly Phe Tyr Tyr Gly Glu Leu
35 40 45
Gly Gly His Arg Gly Leu Val Pro Ala His Leu Leu Asp His Met Ser
50 55 60
<210> 97
<211> 180
<212> DNA
<213> 人工序列
<220>
<223> IRIKS
<220>
<221> CDS
<222> (1)..(180)
<400> 97
cag aag gtg aag acc atc ttc ccc cac acc gcc ggc agc aac aag acc 48
Gln Lys Val Lys Thr Ile Phe Pro His Thr Ala Gly Ser Asn Lys Thr
1 5 10 15
ctg ctg agc ttc gcc cag ggc gac gtg atc acc ctg ctg atc ccc gag 96
Leu Leu Ser Phe Ala Gln Gly Asp Val Ile Thr Leu Leu Ile Pro Glu
20 25 30
gag aag gac ggc tgg ctg tac ggc gag cac gac gtg agc aag gcc aga 144
Glu Lys Asp Gly Trp Leu Tyr Gly Glu His Asp Val Ser Lys Ala Arg
35 40 45
ggc tgg ttc ccc agc agc tac acc aag ctg ctg gag 180
Gly Trp Phe Pro Ser Ser Tyr Thr Lys Leu Leu Glu
50 55 60
<210> 98
<211> 60
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 98
Gln Lys Val Lys Thr Ile Phe Pro His Thr Ala Gly Ser Asn Lys Thr
1 5 10 15
Leu Leu Ser Phe Ala Gln Gly Asp Val Ile Thr Leu Leu Ile Pro Glu
20 25 30
Glu Lys Asp Gly Trp Leu Tyr Gly Glu His Asp Val Ser Lys Ala Arg
35 40 45
Gly Trp Phe Pro Ser Ser Tyr Thr Lys Leu Leu Glu
50 55 60
<210> 99
<211> 174
<212> DNA
<213> 人工序列
<220>
<223> SNX33
<220>
<221> CDS
<222> (1)..(174)
<400> 99
ctg aag ggc aga gcc ctg tac gac ttc cac agc gag aac aag gag gag 48
Leu Lys Gly Arg Ala Leu Tyr Asp Phe His Ser Glu Asn Lys Glu Glu
1 5 10 15
atc agc atc cag cag gac gag gac ctg gtg atc ttc agc gag acc agc 96
Ile Ser Ile Gln Gln Asp Glu Asp Leu Val Ile Phe Ser Glu Thr Ser
20 25 30
ctg gac ggc tgg ctg cag ggc cag aac agc aga ggc gag acc ggc ctg 144
Leu Asp Gly Trp Leu Gln Gly Gln Asn Ser Arg Gly Glu Thr Gly Leu
35 40 45
ttc ccc gcc agc tac gtg gag atc gtg aga 174
Phe Pro Ala Ser Tyr Val Glu Ile Val Arg
50 55
<210> 100
<211> 58
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 100
Leu Lys Gly Arg Ala Leu Tyr Asp Phe His Ser Glu Asn Lys Glu Glu
1 5 10 15
Ile Ser Ile Gln Gln Asp Glu Asp Leu Val Ile Phe Ser Glu Thr Ser
20 25 30
Leu Asp Gly Trp Leu Gln Gly Gln Asn Ser Arg Gly Glu Thr Gly Leu
35 40 45
Phe Pro Ala Ser Tyr Val Glu Ile Val Arg
50 55
<210> 101
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> Eps8L1
<220>
<221> CDS
<222> (1)..(168)
<400> 101
aag tgg gtg ctg tgc aac tac gac ttc cag gcc aga aac agc agc gag 48
Lys Trp Val Leu Cys Asn Tyr Asp Phe Gln Ala Arg Asn Ser Ser Glu
1 5 10 15
ctg agc gtg aag cag aga gac gtg ctg gag gtg ctg gac gac agc aga 96
Leu Ser Val Lys Gln Arg Asp Val Leu Glu Val Leu Asp Asp Ser Arg
20 25 30
aag tgg tgg aag gtg aga gac ccc gcc ggc cag gag ggc tac gtg ccc 144
Lys Trp Trp Lys Val Arg Asp Pro Ala Gly Gln Glu Gly Tyr Val Pro
35 40 45
tac aac atc ctg acc ccc tac ccc 168
Tyr Asn Ile Leu Thr Pro Tyr Pro
50 55
<210> 102
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 102
Lys Trp Val Leu Cys Asn Tyr Asp Phe Gln Ala Arg Asn Ser Ser Glu
1 5 10 15
Leu Ser Val Lys Gln Arg Asp Val Leu Glu Val Leu Asp Asp Ser Arg
20 25 30
Lys Trp Trp Lys Val Arg Asp Pro Ala Gly Gln Glu Gly Tyr Val Pro
35 40 45
Tyr Asn Ile Leu Thr Pro Tyr Pro
50 55
<210> 103
<211> 177
<212> DNA
<213> 人工序列
<220>
<223> FISH#5
<220>
<221> CDS
<222> (1)..(177)
<400> 103
gac gtg tac gtg agc atc gcc gac tac gag ggc gac gag gag acc gcc 48
Asp Val Tyr Val Ser Ile Ala Asp Tyr Glu Gly Asp Glu Glu Thr Ala
1 5 10 15
ggc ttc cag gag ggc gtg agc atg gag gtg ctg gag aga aac ccc aac 96
Gly Phe Gln Glu Gly Val Ser Met Glu Val Leu Glu Arg Asn Pro Asn
20 25 30
ggc tgg tgg tac tgc cag atc ctg gac ggc gtg aag ccc ttc aag ggc 144
Gly Trp Trp Tyr Cys Gln Ile Leu Asp Gly Val Lys Pro Phe Lys Gly
35 40 45
tgg gtg ccc agc aac tac ctg gag aag aag aac 177
Trp Val Pro Ser Asn Tyr Leu Glu Lys Lys Asn
50 55
<210> 104
<211> 59
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 104
Asp Val Tyr Val Ser Ile Ala Asp Tyr Glu Gly Asp Glu Glu Thr Ala
1 5 10 15
Gly Phe Gln Glu Gly Val Ser Met Glu Val Leu Glu Arg Asn Pro Asn
20 25 30
Gly Trp Trp Tyr Cys Gln Ile Leu Asp Gly Val Lys Pro Phe Lys Gly
35 40 45
Trp Val Pro Ser Asn Tyr Leu Glu Lys Lys Asn
50 55
<210> 105
<211> 171
<212> DNA
<213> 人工序列
<220>
<223> CMS#1
<220>
<221> CDS
<222> (1)..(171)
<400> 105
gtg gac tac atc gtg gag tac gac tac gac gcc gtg cac gac gac gag 48
Val Asp Tyr Ile Val Glu Tyr Asp Tyr Asp Ala Val His Asp Asp Glu
1 5 10 15
ctg acc atc aga gtg ggc gag atc atc aga aac gtg aag aag ctg cag 96
Leu Thr Ile Arg Val Gly Glu Ile Ile Arg Asn Val Lys Lys Leu Gln
20 25 30
gag gag ggc tgg ctg gag ggc gag ctg aac ggc aga aga ggc atg ttc 144
Glu Glu Gly Trp Leu Glu Gly Glu Leu Asn Gly Arg Arg Gly Met Phe
35 40 45
ccc gac aac ttc gtg aag gag atc aag 171
Pro Asp Asn Phe Val Lys Glu Ile Lys
50 55
<210> 106
<211> 57
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 106
Val Asp Tyr Ile Val Glu Tyr Asp Tyr Asp Ala Val His Asp Asp Glu
1 5 10 15
Leu Thr Ile Arg Val Gly Glu Ile Ile Arg Asn Val Lys Lys Leu Gln
20 25 30
Glu Glu Gly Trp Leu Glu Gly Glu Leu Asn Gly Arg Arg Gly Met Phe
35 40 45
Pro Asp Asn Phe Val Lys Glu Ile Lys
50 55
<210> 107
<211> 168
<212> DNA
<213> 人工序列
<220>
<223> OSTF1
<220>
<221> CDS
<222> (1)..(168)
<400> 107
aag gtg ttc aga gcc ctg tac acc ttc gag ccc aga acc ccc gac gag 48
Lys Val Phe Arg Ala Leu Tyr Thr Phe Glu Pro Arg Thr Pro Asp Glu
1 5 10 15
ctg tac ttc gag gag ggc gac atc atc tac atc acc gac atg agc gac 96
Leu Tyr Phe Glu Glu Gly Asp Ile Ile Tyr Ile Thr Asp Met Ser Asp
20 25 30
acc aac tgg tgg aag ggc acc agc aag ggc aga acc ggc ctg atc ccc 144
Thr Asn Trp Trp Lys Gly Thr Ser Lys Gly Arg Thr Gly Leu Ile Pro
35 40 45
agc aac tac gtg gcc gag cag gcc 168
Ser Asn Tyr Val Ala Glu Gln Ala
50 55
<210> 108
<211> 56
<212> PRT
<213> 人工序列
<220>
<223> 合成的构建体
<400> 108
Lys Val Phe Arg Ala Leu Tyr Thr Phe Glu Pro Arg Thr Pro Asp Glu
1 5 10 15
Leu Tyr Phe Glu Glu Gly Asp Ile Ile Tyr Ile Thr Asp Met Ser Asp
20 25 30
Thr Asn Trp Trp Lys Gly Thr Ser Lys Gly Arg Thr Gly Leu Ile Pro
35 40 45
Ser Asn Tyr Val Ala Glu Gln Ala
50 55
<210> 109
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> Cysknots/Knottin
<400> 109
Cys Ser Pro Ser Gly Ala Ile Cys Ser Gly Phe Gly Pro Pro Glu Gln
1 5 10 15
Cys Cys Ser Ala Gly Cys Val Leu Asn Arg Arg Ala Arg Ser Trp Arg
20 25 30
Cys Gln
<210> 110
<211> 35
<212> PRT
<213> 人工序列
<220>
<223> Cysknots/Knottin (SOTI-III)
<400> 110
Cys Ser Pro Ser Gly Ala Ile Cys Ser Gly Phe Gly Pro Pro Glu Gln
1 5 10 15
Cys Cys Ser Ala Gly Ala Cys Val Pro His Pro Ile Leu Arg Ile Phe
20 25 30
Val Cys Gln
35
<210> 111
<211> 29
<212> PRT
<213> 人工序列
<220>
<223> Kalata B1
<400> 111
Gly Leu Pro Val Cys Gly Glu Thr Cys Val Gly Gly Thr Cys Asn Thr
1 5 10 15
Pro Gly Cys Thr Cys Ser Trp Pro Val Cys Thr Arg Asn
20 25
<210> 112
<211> 29
<212> PRT
<213> 人工序列
<220>
<223> Kalata B2
<400> 112
Gly Leu Pro Val Cys Gly Glu Thr Cys Phe Gly Gly Thr Cys Asn Thr
1 5 10 15
Pro Gly Cys Ser Cys Thr Trp Pro Ile Cys Thr Arg Asp
20 25
<210> 113
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> MCoTI-I
<400> 113
Gly Gly Val Cys Pro Lys Ile Leu Gln Arg Cys Arg Arg Asp Ser Asp
1 5 10 15
Cys Pro Gly Ala Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly Ser Gly
20 25 30
Ser Asp
<210> 114
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> MCoTI-II
<400> 114
Gly Gly Val Cys Pro Lys Ile Leu Lys Lys Cys Arg Arg Asp Ser Asp
1 5 10 15
Cys Pro Gly Ala Cys Ile Cys Arg Gly Asn Gly Tyr Cys Gly Ser Gly
20 25 30
Ser Asp
<210> 115
<211> 63
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD8跨膜结构域
<400> 115
atctgggcac ccttggccgg aatctgcgtg gcccttctgc tgtccttgat catcactctc 60
atc 63
<210> 116
<211> 81
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD28跨膜结构域
<400> 116
ttttgggcac tggtcgtggt tgctggagtc ctgttttgtt atggcttgct agtgacagtg 60
gctctttgtg ttatctggac a 81
<210> 117
<211> 135
<212> DNA
<213> 人工序列
<220>
<223> 鼠4-1BB细胞内结构域
<400> 117
aaatggatca ggaaaaaatt cccccacata ttcaagcaac catttaagaa gaccactgga 60
gcagctcaag aggaagatgc ttgtagctgc cgatgtccac aggaagaaga aggaggagga 120
ggaggctatg agctg 135
<210> 118
<211> 123
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD28细胞内结构域
<400> 118
aatagtagaa ggaacagact ccttcaaagt gactacatga acatgactcc ccggaggcct 60
gggctcactc gaaagcctta ccagccctac gcccctgcca gagactttgc agcgtaccgc 120
ccc 123
<210> 119
<211> 336
<212> DNA
<213> 人工序列
<220>
<223> 鼠CD3ζ细胞内结构域
<400> 119
agagcaaaat tcagcaggag tgcagagact gctgccaacc tgcaggaccc caaccagctc 60
tacaatgagc tcaatctagg gcgaagagag gaatatgacg tcttggagaa gaagcgggct 120
cgggatccag agatgggagg caaacagcag aggaggagga acccccagga aggcgtatac 180
aatgcactgc agaaagacaa gatggcagaa gcctacagtg agatcggcac aaaaggcgag 240
aggcggagag gcaaggggca cgatggcctt taccagggtc tcagcactgc caccaaggac 300
acctatgatg ccctgcatat gcagaccctg gcccct 336
<210> 120
<211> 19
<212> DNA
<213> 人工序列
<220>
<223> MLV-U3正向引物
<400> 120
agcccacaac ccctcactc 19
<210> 121
<211> 18
<212> DNA
<213> 人工序列
<220>
<223> MLV-Psi反向引物
<400> 121
tctcccgatc ccggacga 18
<210> 122
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> 扩增探针
<400> 122
ccccaaatga aagacccccg ctgacg 26
Claims (50)
1.一种用于施用给受试者的药物组合物，所述药物组合物包含：
病毒载体，其含有编码具有免疫活化效应的产物的异源多核苷酸，
其中所述病毒载体转导或整合进所述受试者的血细胞中。
2.权利要求1的药物组合物，其中所述受试者是哺乳动物。
3.权利要求2的药物组合物，其中所述哺乳动物是人。
4.权利要求1的药物组合物，其中腹膜内地施用所述组合物。
5.权利要求1的药物组合物，其中血管内地施用所述组合物。
6.权利要求1的药物组合物，其中所述病毒载体是逆转录病毒载体。
7.权利要求6的药物组合物，其中所述逆转录病毒载体选自：γ逆转录病毒载体、β逆转录病毒载体、α逆转录病毒载体、慢病毒载体和泡沫病毒载体。
8.权利要求7的药物组合物，其中所述逆转录病毒载体是复制型逆转录病毒载体(RRV)。
9.权利要求8的药物组合物，其中所述RRV包含：γ逆转录病毒GAG蛋白；γ逆转录病毒POL蛋白；γ逆转录病毒包膜；γ逆转录病毒RNA多核苷酸，其包含在γ逆转录病毒多核苷酸序列的3'末端处的来自鼠白血病病毒(MLV)、莫洛尼鼠白血病病毒(MoMLV)、猫白血病病毒(FeLV)、狒狒内源性逆转录病毒(BEV)、猪内源性病毒(PERV)、猫衍生的逆转录病毒RD114、松鼠猴逆转录病毒、嗜异性鼠白血病病毒相关病毒(XMRV)、禽网状内皮组织增殖病病毒(REV)或长臂猿白血病病毒(GALV)的3'非翻译区(U3)和重复区域(R)序列，在γ逆转录病毒多核苷酸的5'末端处的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的R和5'非翻译区(U5)序列，位于U5和U3区域之间的来自MLV、MoMLV、FeLV、BEV、PERV、RD114、松鼠猴逆转录病毒、XMRV、REV或GALV的gag核酸结构域、pol核酸结构域和env核酸结构域；包含内部核糖体进入位点(IRES)、小启动子或2A或2A-样序列的盒，其在编码具有免疫活化效应的产物的异源多核苷酸的上游并与其可操作地连接，其中所述盒位于U3区域的5'侧和env核酸结构域的3'侧；以及在靶细胞中的逆转录、包装和整合所必需的顺式作用序列。
10.权利要求9的药物组合物，其中从MLV工程改造RRV。
11.权利要求7的药物组合物，其中所述病毒载体是非复制病毒载体(RNV)。
12.权利要求11的药物组合物，其中所述RNV包含：
包含包膜蛋白和脂质膜的包膜；
被包含在所述包膜内的核酸，所述核酸包含特定序列，所述特定序列从5’至3’包含：
SEQ ID NO:12的核苷酸1-1050或与其具有至少85％同一性的序列；
编码具有免疫活化效应的产物的RNA序列；和
SEQ ID NO:12的核苷酸1101-1662或与其具有至少85％同一性的序列，
其中所述RNV可以感染分裂中的细胞且其中所述编码具有免疫活化效应的产物的RNA序列整合进分裂中的细胞中。
13.前述权利要求中的任一项的药物组合物，其中所述免疫活化效应是免疫介导的活性。
14.权利要求1-12中的任一项的药物组合物，其中所述血细胞是T-细胞或T-细胞前体。
15.权利要求1-12中的任一项的药物组合物，其中所述异源多核苷酸编码嵌合抗原受体(CAR)或CAR-样分子。
16.权利要求15的药物组合物，其中所述CAR或CAR-样分子包含抗原结合结构域、任选的间隔物、跨膜结构域和任选的细胞内结构域。
17.权利要求16的药物组合物，其中所述抗原结合结构域是非免疫球蛋白结合结构域。
18.权利要求17的药物组合物，其中所述非免疫球蛋白结合结构域包含支架蛋白。
19.权利要求16的药物组合物，其中所述跨膜结构域是CD28跨膜结构域。
20.权利要求16的药物组合物，其中所述跨膜结构域是CD8跨膜结构域。
21.权利要求20的药物组合物，其中所述CD8跨膜结构域由与SEQ ID NO:1具有98％至100％同一性的序列编码。
22.权利要求16的药物组合物，其中所述抗原结合结构域包含scFv或抗体片段。
23.权利要求16的药物组合物，其中所述任选的间隔物由与SEQ ID NO:2具有至少98％同一性的序列编码。
24.权利要求16的药物组合物，其中所述任选的细胞内结构域包含CD3ζ结构域。
25.权利要求16的药物组合物，其中所述任选的细胞内结构域包含41BB或CD28细胞内结构域。
26.权利要求25的药物组合物，其中所述41BB结构域由与SEQ ID NO:5具有98％至100％同一性的的序列编码。
27.权利要求24的药物组合物，其中所述CD3ζ结构域由与SEQ ID NO:4具有至少98％同一性的序列编码。
28.权利要求16的药物组合物，其中所述抗原结合结构域特异性地结合选自以下的抗原：
CD5、CD19；CD123；CD22；CD30；CD171；CS1(也被称作CD2子集1、CRACC、SLAMF7、CD319和19A24)；C-型凝集素-样分子-1(CLL-1或CLECL1)；CD33；表皮生长因子受体变体III(EGFRviii)；神经节苷脂G2(GD2)；神经节苷脂GD3(aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer)；TNF受体家族成员B细胞成熟(BCMA)；Tn抗原((Tn Ag)或(GalNAcα-Ser/Thr))；前列腺特异性的膜抗原(PSMA)；受体酪氨酸激酶-样孤儿受体1(ROR1)；Fms样酪氨酸激酶3(FLT3)；肿瘤相关的糖蛋白72(TAG72)；CD38；CD44v6；在急性白血病或淋巴瘤上表达、但不在造血祖细胞上表达的糖基化的CD43表位，在非造血癌上表达的糖基化的CD43表位，癌胚抗原(CEA)；上皮细胞粘附分子(EPCAM)；B7H3(CD276)；KIT(CD117)；白介素-13受体亚基α-2(IL-13Ra2或CD213A2)；间皮素；白介素11受体α(IL-llRa)；前列腺干细胞抗原(PSCA)；蛋白酶丝氨酸21(睾蛋白或PRSS21)；血管内皮生长因子受体2(VEGFR2)；Lewis(Y)抗原；CD24；血小板-衍生的生长因子受体β(PDGFR-β)；阶段特异性的胚胎抗原-4(SSEA-4)；CD20；叶酸盐受体α(FRa或FR1)；叶酸盐受体β(FRb)；受体酪氨酸-蛋白激酶ERBB2(Her2/neu)；细胞表面相关的粘蛋白1(MUC1)；表皮生长因子受体(EGFR)；神经细胞粘附分子(NCAM)；前列腺酶；前列腺酸性磷酸酶(PAP)；突变的延伸因子2(ELF2M)；Ephrin B2；成纤维细胞活化蛋白α(FAP)；胰岛素-样生长因子1受体(IGF-I受体),碳酸酐酶IX(CAlX)；蛋白酶体(Prosome,Macropain)亚基,β类型,9(LMP2)；糖蛋白100(gpl00)；由裂点簇区(BCR)和Abelson鼠白血病病毒癌基因同系物1(Abl)组成的癌基因融合蛋白(bcr-abl)；酪氨酸酶；ephrin A型受体2(EphA2)；唾液酸基Lewis粘附分子(sLe)；神经节苷脂GM3(aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(l-1)Cer)；转谷氨酰胺酶5(TGS5)；高分子量-黑素瘤相关抗原(HMWMAA)；o-乙酰基-GD2神经节苷脂(OAcGD2)；肿瘤内皮标志物1(TEM1/CD248)；肿瘤内皮标志物7相关的(TEM7R)；封闭蛋白6(CLDN6)；促甲状腺激素受体(TSHR)；G蛋白偶联受体C类5组,成员D(GPRC5D)；染色体X开放读码框61(CXORF61)；CD97；CD179a；间变性淋巴瘤激酶(ALK)；聚唾液酸；胎盘特异性的1(PLAC1)；globoH糖神经酰胺的己糖部分(GloboH)；乳腺分化抗原(NY-BR-1)；uroplakin 2(UPK2)；甲型肝炎病毒细胞受体1(HAVCR1)；肾上腺素受体β3(ADRB3)；pannexin 3(PANX3)；G蛋白偶联受体20(GPR20)；淋巴细胞抗原6复合物,基因座K9(LY6K)；嗅觉受体51E2(OR51E2)；TCRγ交替读码框蛋白(TARP)；肾母细胞瘤蛋白(WT1)；癌症/睾丸抗原1(NY-ES0-1)；癌症/睾丸抗原2(LAGE-1a)；黑素瘤相关抗原1(MAGE-A1)；位于染色体12p上的ETS易位-变体基因6(ETV6-AML)；精子蛋白17(SPA17)；X抗原家族,成员lA(XAGEl)；结合血管生成素的细胞表面受体2(Tie 2)；黑素瘤癌症睾丸抗原-1(MAD-CT-1)；黑素瘤癌症睾丸抗原-2(MAD-CT-2)；Fos相关抗原1；肿瘤蛋白p53(p53)；p53突变体；prostein；存活素；端粒末端转移酶；前列腺癌肿瘤抗原-1(PCT A-1或半乳糖凝集素8),被T细胞1识别的黑素瘤抗原(MelanA或MARTI)；大鼠肉瘤(Ras)突变体；人端粒末端转移酶逆转录酶(hTERT)；肉瘤易位断点；细胞凋亡的黑素瘤抑制剂(ML-IAP)；ERG(跨膜蛋白酶,丝氨酸2(TMPRSS2)ETS融合基因)；N-乙酰基葡糖胺基-转移酶V(NA17)；成对的盒蛋白Pax-3(PAX3)；雄激素受体；细胞周期蛋白Bl；v-myc禽髓细胞瘤病病毒癌基因神经母细胞瘤衍生的同系物(MYCN)；Ras同系物家族成员C(RhoC)；酪氨酸酶相关蛋白2(TRP-2)；细胞色素P450lB 1(CYPlB 1)；CCCTC-结合因子(锌指蛋白)-样(BORIS或印迹位点的调节剂的同系物),被T细胞3识别的鳞状细胞癌抗原(SART3)；成对的盒蛋白Pax-5(PAX5)；顶体蛋白原结合蛋白sp32(OY-TESl)；淋巴细胞特异性的蛋白酪氨酸激酶(LCK)；A激酶锚蛋白4(AKAP-4)；滑膜肉瘤,X断点2(SSX2)；高级糖化终产物的受体(RAGE-1)；肾遍布物1(RUl)；肾遍布物2(RU2)；legumain；人乳头瘤病毒E6(HPV E6)；人乳头瘤病毒E7(HPV E7)；肠羧基酯酶；突变的热激蛋白70-2(mut hsp70-2)；CD79a；CD79b；CD72；白细胞-相关的免疫球蛋白-样受体1(LAIRl)；IgA受体的Fc片段(FCAR或CD89)；白细胞免疫球蛋白-样受体亚家族A成员2(LILRA2)；CD300分子-样家族成员f(CD300LF)；C-型凝集素结构域家族12成员A(CLEC12A)；骨髓间质细胞抗原2(BST2)；含有EGF-样模块的粘蛋白-样激素受体-样2(EMR2)；淋巴细胞抗原75(LY75)；磷脂酰肌醇蛋白聚糖-3(GPC3)；Fc受体-样5(FCRL5)；和免疫球蛋白λ-样多肽1(IGLLl),MPL,生物素,c-MYC表位标签,CD34,LAMP1 TROP2,GFRα4,CDH17,CDH6,NYBR1,CDH19,CD200R,Slea(CA19.9；唾液酸基Lewis抗原)；岩藻糖基-GM1,PTK7,gpNMB,CDH1-CD324,DLL3,CD276/B7H3,IL11Ra,IL13Ra2,CD179b-IGLl1,TCRγ-δ,NKG2D,CD32(FCGR2A),Tn ag,Tim1-/HVCR1,CSF2RA(GM-CSFR-α),TGFβR2,Lews Ag,TCR-β1链,TCR-β2链,TCR-γ链,TCR-δ链,FITC,促黄体激素受体(LHR),促卵泡激素受体(FSHR),促性腺素激素受体(CGHR或GR),CCR4,GD3,SLAMF6,SLAMF4,HIV1包膜糖蛋白,HTLV1-Tax,CMV pp65,EBV-EBNA3c,KSHV K8.1,KSHV-gH,甲型流感血凝素(HA),GAD,PDL1,鸟苷酸环化酶C(GCC),针对桥粒核心糖蛋白3(Dsg3)的自身抗体,针对桥粒核心糖蛋白1(Dsg1)的自身抗体,HLA,HLA-A,HLA-A2,HLA-B,HLA-C,HLA-DP,HLA-DM,HLA-DOA,HLA-DOB,HLA-DQ,HLA-DR,HLA-G,IgE,CD99,Ras G12V,组织因子1(TF1),AFP,GPRC5D,封闭蛋白18.2(CLD18A2或CLDN18A.2)),P-糖蛋白,STEAP1,Liv1,连接素-4,Cripto,gpA33,BST1/CD157,低电导氯离子通道,和被TNT抗体识别的抗原。
29.根据权利要求1所述的药物组合物，其中所述病毒载体包含自失活核酸序列(SIN)。
30.根据权利要求1所述的药物组合物，其中所述病毒载体通过选自SEQ ID NO:18、19、20、21和22的序列的表达而产生。
31.一种非复制病毒载体，其包含：
包含包膜蛋白和脂质膜的包膜；
被包含在所述包膜内的核酸，所述核酸包含特定序列，所述特定序列从5’至3’包含：
SEQ ID NO:12的核苷酸1-1050或与其具有至少85％同一性的序列；
编码嵌合抗原受体(CAR)的RNA序列；和
SEQ ID NO:12的核苷酸1101-1662或与其具有至少85％同一性的序列，
其中所述RNV可以感染分裂中的细胞且其中所述编码嵌合抗原受体的RNA序列整合进分裂中的细胞中。
32.权利要求31的RNVCAR，其中所述CAR包含抗原结合结构域、任选的间隔物、跨膜结构域和任选的细胞内结构域。
33.权利要求32的RNVCAR，其中所述跨膜结构域是CD28跨膜结构域。
34.权利要求32的RNVCAR，其中所述跨膜结构域是CD8跨膜结构域。
35.权利要求34的RNVCAR，其中所述CD8跨膜结构域由与SEQ ID NO:1具有98％至100％同一性的的序列编码。
36.权利要求32的RNVCAR，其中所述抗原结合结构域包含scFv或抗体片段或非免疫球蛋白结合结构域。
37.权利要求32的RNVCAR，其中所述任选的间隔物由与SEQ ID NO:2具有至少98％同一性的序列编码。
38.权利要求32的RNVCAR，其中所述细胞内结构域包含CD3ζ结构域。
39.权利要求32的RNVCAR，其中所述细胞内结构域包含41BB或CD28细胞内结构域。
40.权利要求39的RNVCAR，其中所述41BB结构域由与SEQ ID NO:5具有85％至100％同一性的序列编码。
41.权利要求38的RNVCAR，其中所述CD3ζ结构域由与SEQ ID NO:4具有至少98％同一性的序列编码。
42.权利要求31的RNVCAR，其中所述编码嵌合抗原受体的RNA序列包含SEQ ID NO:13-17中的任一个，其中T是U。
43.权利要求32的RNVCAR，其中所述抗原结合结构域特异性地结合选自以下的抗原：
CD5、CD19；CD123；CD22；CD30；CD171；CS1(也被称作CD2子集1、CRACC、SLAMF7、CD319和19A24)；C-型凝集素-样分子-1(CLL-1或CLECL1)；CD33；表皮生长因子受体变体III(EGFRviii)；神经节苷脂G2(GD2)；神经节苷脂GD3(aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4)bDGlcp(l-l)Cer)；TNF受体家族成员B细胞成熟(BCMA)；Tn抗原((Tn Ag)或(GalNAcα-Ser/Thr))；前列腺特异性的膜抗原(PSMA)；受体酪氨酸激酶-样孤儿受体1(ROR1)；Fms样酪氨酸激酶3(FLT3)；肿瘤相关的糖蛋白72(TAG72)；CD38；CD44v6；在急性白血病或淋巴瘤上表达、但不在造血祖细胞上表达的糖基化的CD43表位，在非造血癌上表达的糖基化的CD43表位，癌胚抗原(CEA)；上皮细胞粘附分子(EPCAM)；B7H3(CD276)；KIT(CD117)；白介素-13受体亚基α-2(IL-13Ra2或CD213A2)；间皮素；白介素11受体α(IL-llRa)；前列腺干细胞抗原(PSCA)；蛋白酶丝氨酸21(睾蛋白或PRSS21)；血管内皮生长因子受体2(VEGFR2)；Lewis(Y)抗原；CD24；血小板-衍生的生长因子受体β(PDGFR-β)；阶段特异性的胚胎抗原-4(SSEA-4)；CD20；叶酸盐受体α(FRa或FR1)；叶酸盐受体β(FRb)；受体酪氨酸-蛋白激酶ERBB2(Her2/neu)；细胞表面相关的粘蛋白1(MUC1)；表皮生长因子受体(EGFR)；神经细胞粘附分子(NCAM)；前列腺酶；前列腺酸性磷酸酶(PAP)；突变的延伸因子2(ELF2M)；Ephrin B2；成纤维细胞活化蛋白α(FAP)；胰岛素-样生长因子1受体(IGF-I受体),碳酸酐酶IX(CAlX)；蛋白酶体(Prosome,Macropain)亚基,β类型,9(LMP2)；糖蛋白100(gpl00)；由裂点簇区(BCR)和Abelson鼠白血病病毒癌基因同系物1(Abl)组成的癌基因融合蛋白(bcr-abl)；酪氨酸酶；ephrin A型受体2(EphA2)；唾液酸基Lewis粘附分子(sLe)；神经节苷脂GM3(aNeu5Ac(2-3)bDClalp(l-4)bDGlcp(l-1)Cer)；转谷氨酰胺酶5(TGS5)；高分子量-黑素瘤相关抗原(HMWMAA)；o-乙酰基-GD2神经节苷脂(OAcGD2)；肿瘤内皮标志物1(TEM1/CD248)；肿瘤内皮标志物7相关的(TEM7R)；封闭蛋白6(CLDN6)；促甲状腺激素受体(TSHR)；G蛋白偶联受体C类5组,成员D(GPRC5D)；染色体X开放读码框61(CXORF61)；CD97；CD179a；间变性淋巴瘤激酶(ALK)；聚唾液酸；胎盘特异性的1(PLAC1)；globoH糖神经酰胺的己糖部分(GloboH)；乳腺分化抗原(NY-BR-1)；uroplakin 2(UPK2)；甲型肝炎病毒细胞受体1(HAVCR1)；肾上腺素受体β3(ADRB3)；pannexin 3(PANX3)；G蛋白偶联受体20(GPR20)；淋巴细胞抗原6复合物,基因座K9(LY6K)；嗅觉受体51E2(OR51E2)；TCRγ交替读码框蛋白(TARP)；肾母细胞瘤蛋白(WT1)；癌症/睾丸抗原1(NY-ES0-1)；癌症/睾丸抗原2(LAGE-1a)；黑素瘤相关抗原1(MAGE-A1)；位于染色体12p上的ETS易位-变体基因6(ETV6-AML)；精子蛋白17(SPA17)；X抗原家族,成员lA(XAGEl)；结合血管生成素的细胞表面受体2(Tie 2)；黑素瘤癌症睾丸抗原-1(MAD-CT-1)；黑素瘤癌症睾丸抗原-2(MAD-CT-2)；Fos相关抗原1；肿瘤蛋白p53(p53)；p53突变体；prostein；存活素；端粒末端转移酶；前列腺癌肿瘤抗原-1(PCT A-1或半乳糖凝集素8),被T细胞1识别的黑素瘤抗原(MelanA或MARTI)；大鼠肉瘤(Ras)突变体；人端粒末端转移酶逆转录酶(hTERT)；肉瘤易位断点；细胞凋亡的黑素瘤抑制剂(ML-IAP)；ERG(跨膜蛋白酶,丝氨酸2(TMPRSS2)ETS融合基因)；N-乙酰基葡糖胺基-转移酶V(NA17)；成对的盒蛋白Pax-3(PAX3)；雄激素受体；细胞周期蛋白Bl；v-myc禽髓细胞瘤病病毒癌基因神经母细胞瘤衍生的同系物(MYCN)；Ras同系物家族成员C(RhoC)；酪氨酸酶相关蛋白2(TRP-2)；细胞色素P450lB 1(CYPlB 1)；CCCTC-结合因子(锌指蛋白)-样(BORIS或印迹位点的调节剂的同系物),被T细胞3识别的鳞状细胞癌抗原(SART3)；成对的盒蛋白Pax-5(PAX5)；顶体蛋白原结合蛋白sp32(OY-TESl)；淋巴细胞特异性的蛋白酪氨酸激酶(LCK)；A激酶锚蛋白4(AKAP-4)；滑膜肉瘤,X断点2(SSX2)；高级糖化终产物的受体(RAGE-1)；肾遍布物1(RUl)；肾遍布物2(RU2)；legumain；人乳头瘤病毒E6(HPV E6)；人乳头瘤病毒E7(HPV E7)；肠羧基酯酶；突变的热激蛋白70-2(mut hsp70-2)；CD79a；CD79b；CD72；白细胞-相关的免疫球蛋白-样受体1(LAIRl)；IgA受体的Fc片段(FCAR或CD89)；白细胞免疫球蛋白-样受体亚家族A成员2(LILRA2)；CD300分子-样家族成员f(CD300LF)；C-型凝集素结构域家族12成员A(CLEC12A)；骨髓间质细胞抗原2(BST2)；含有EGF-样模块的粘蛋白-样激素受体-样2(EMR2)；淋巴细胞抗原75(LY75)；磷脂酰肌醇蛋白聚糖-3(GPC3)；Fc受体-样5(FCRL5)；和免疫球蛋白λ-样多肽1(IGLLl),MPL,生物素,c-MYC表位标签,CD34,LAMP1 TROP2,GFRα4,CDH17,CDH6,NYBR1,CDH19,CD200R,Slea(CA19.9；唾液酸基Lewis抗原)；岩藻糖基-GM1,PTK7,gpNMB,CDH1-CD324,DLL3,CD276/B7H3,IL11Ra,IL13Ra2,CD179b-IGLl1,TCRγ-δ,NKG2D,CD32(FCGR2A),Tn ag,Tim1-/HVCR1,CSF2RA(GM-CSFR-α),TGFβR2,Lews Ag,TCR-β1链,TCR-β2链,TCR-γ链,TCR-δ链,FITC,促黄体激素受体(LHR),促卵泡激素受体(FSHR),促性腺素激素受体(CGHR或GR),CCR4,GD3,SLAMF6,SLAMF4,HIV1包膜糖蛋白,HTLV1-Tax,CMV pp65,EBV-EBNA3c,KSHV K8.1,KSHV-gH,甲型流感血凝素(HA),GAD,PDL1,鸟苷酸环化酶C(GCC),针对桥粒核心糖蛋白3(Dsg3)的自身抗体,针对桥粒核心糖蛋白1(Dsg1)的自身抗体,HLA,HLA-A,HLA-A2,HLA-B,HLA-C,HLA-DP,HLA-DM,HLA-DOA,HLA-DOB,HLA-DQ,HLA-DR,HLA-G,IgE,CD99,Ras G12V,组织因子1(TF1),AFP,GPRC5D,封闭蛋白18.2(CLD18A2或CLDN18A.2)),P-糖蛋白,STEAP1,Liv1,连接素-4,Cripto,gpA33,BST1/CD157,低电导氯离子通道,和被TNT抗体识别的抗原。
44.权利要求31的RNVCAR，其进一步包含与异源多核苷酸可操作地连接的IRES或2A肽盒。
45.权利要求44的RNVCAR，其中所述异源多核苷酸编码前药活化剂酶。
46.权利要求45的RNVCAR，其中所述前药活化剂酶是胞嘧啶脱氨酶或胸苷激酶。
47.权利要求31-43中的任一项的RNVCAR，其如下产生：用质粒转染包装细胞系，所述质粒包含含有嵌合抗原受体编码序列的SEQ ID NO:3，培养所述包装细胞以产生RNVCAR，和分离RNVCAR。
48.权利要求47的RNVCAR，其中所述质粒包含选自SEQ ID NO:18至22的序列。
49.一种给受试者提供过继细胞疗法的方法，其包括：
给所述受试者施用权利要求1-12中的任一项的药物组合物或权利要求31-43中的任一项的RNVCAR。
50.根据权利要求49所述的方法，其中在施用RNVCAR之前或同时用药剂处理所述受试者以活化T-细胞。
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998000541A2 (en) * | 1996-07-03 | 1998-01-08 | Chiron Corporation | Methods for administration of recombinant gene delivery vehicles for treatment of human disease |
| WO2000065034A2 (en) * | 1999-04-23 | 2000-11-02 | Centre For Translational Research In Cancer | Pseudotyped retroviral vector for gene therapy of cancer |
| WO2012079000A1 (en) * | 2010-12-09 | 2012-06-14 | The Trustees Of The University Of Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| US20160333373A1 (en) * | 2013-12-20 | 2016-11-17 | Oxford Biomedica (Uk) Limited | Viral Vector Production System |
| US20170175137A1 (en) * | 2014-03-26 | 2017-06-22 | Tocagen Inc. | Retroviral vector having immune-stimulating activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130266551A1 (en) * | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| JP7088932B2 (ja) * | 2016-09-14 | 2022-06-21 | ヤンセン バイオテツク，インコーポレーテツド | Ｂｃｍａ特異的フィブロネクチンｉｉｉ型ドメインを有するキメラ抗原受容体、及びその使用 |
| US20200215111A1 (en) * | 2017-06-30 | 2020-07-09 | Memorial Sloan Kettering Cancer Center | Compositions and methods for adoptive cell therapy for cancer |
-
2020
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-
2021
- 2021-06-07 ZA ZA2021/03899A patent/ZA202103899B/en unknown
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998000541A2 (en) * | 1996-07-03 | 1998-01-08 | Chiron Corporation | Methods for administration of recombinant gene delivery vehicles for treatment of human disease |
| WO2000065034A2 (en) * | 1999-04-23 | 2000-11-02 | Centre For Translational Research In Cancer | Pseudotyped retroviral vector for gene therapy of cancer |
| WO2012079000A1 (en) * | 2010-12-09 | 2012-06-14 | The Trustees Of The University Of Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| US20160333373A1 (en) * | 2013-12-20 | 2016-11-17 | Oxford Biomedica (Uk) Limited | Viral Vector Production System |
| US20170175137A1 (en) * | 2014-03-26 | 2017-06-22 | Tocagen Inc. | Retroviral vector having immune-stimulating activity |
Non-Patent Citations (3)
| Title |
|---|
| BRUCE L LECINE等: "Global Manufacturing of CAR T Cell Therapy", 《MOL THER METHODS CLIN DEV.》, vol. 4, 31 December 2016 (2016-12-31), pages 92 - 101, XP055510414, DOI: 10.1016/j.omtm.2016.12.006 * |
| PHILIP L. SHERIDAN等: "Generation of Retroviral Packaging and Producer Cell Lines for Large-Scale Vector Production and Clinical Application:Improved Safety and High Titer", 《MOLECULAR THERAPY》, vol. 2, no. 3, 27 March 2000 (2000-03-27), pages 262 - 275, XP055547590, DOI: 10.1006/mthe.2000.0123 * |
| 伍新尧: "《分子遗传学与基因工程》", 31 December 1997, 郑州：河南医科大学出版社, pages: 246 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117567650A (zh) * | 2024-01-15 | 2024-02-20 | 中国人民解放军东部战区总医院 | 共表达细胞间黏附分子icam2的car-t细胞及其制备方法与应用 |
| CN117567650B (zh) * | 2024-01-15 | 2024-04-02 | 中国人民解放军东部战区总医院 | 共表达细胞间黏附分子icam2的car-t细胞及其制备方法与应用 |
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