CN108135998B - 高亲合力hpv t细胞受体 - Google Patents
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Abstract
本公开提供了对HPV 16/18的蛋白E5、E6和E7具有选择性和特异性的基于T细胞受体(TCR)的分子。TCR可用于诊断、治疗和预防HPV感染以及用于诊断、治疗和预防HPV感染。
Description
发明领域
本发明涉及针对人***瘤病毒抗原的新型高亲合力抗原识别构建体。本发明提供了对HPV 16/18的蛋白E5、E6和E7具有选择性和特异性的新型的基于T细胞受体(TCR)的分子。本发明的TCR及来源于其的HPV抗原结合片段可用于诊断、治疗和预防HPV感染以及用于诊断、治疗和预防HPV感染介导的继发病如HPV感染引起的癌症,诸如***、鼻咽癌或头颈癌。还提供了编码本发明蛋白质的核酸以及表达其的重组细胞。
描述
TCR是免疫球蛋白超家族的异二聚体细胞表面蛋白,其与参与介导信号转导的CD3复合物的不变的蛋白相关。TCR以αβ和γδ形式存在,它们在结构上类似,但是具有相当不同的解剖学位置和可能地功能。天然异二聚体αβTCR的细胞外部分由两条多肽组成,每条多肽具有膜近端恒定结构域和膜-远端可变结构域。恒定结构域和可变结构域中的每一个包括链内二硫键。可变结构域含有与抗体的互补决定区(CDR)类似的高度多态性环。使用TCR基因疗法克服了许多当前的障碍。它允许使患者自身的T细胞配备所需的特异性,并在很短的时间段内产生足够量的T细胞,从而避免其耗竭。TCR将被转导到中央记忆型T细胞或具有干细胞特征的T细胞中,这可以确保一经转移更好的持久性和功能。TCR工程化的T细胞将被输注到通过化学疗法或辐射使淋巴细胞减少的癌症患者中,从而允许有效植入但抑制免疫抑制。
人***瘤病毒(HPV)是感染皮肤上皮和/或粘膜上皮的小型无包膜双链DNA病毒。已知存在超过100种HPV基因型。感染男性和女性***生殖道的向粘膜性HPV亚群是最常见的性传播的人类病原体。这些性传播的向粘膜性HPV根据它们的致癌性被进一步细分为高风险(如HPV16和HPV18)或低风险(HPV6和HPV11)。高风险基因型与***与生殖器癌有因果关系,所述***与生殖器癌包括近100%的***,其是全球女性因癌症死亡的第二大原因。
致癌HPV的持续性对于宫颈初癌和癌症的发展是必需的。然而,尚未完全了解决定病毒持续性和致瘤性进展的因素。病毒感染后***变的初始事件取决于以下事实:高风险HPV类型经历特定变化,其消除了在被感染的角化细胞中病毒基因表达的转录控制。这些细胞控制功能的失活允许早期病毒基因E6和E7的转录失调,从而触发细胞增殖、细胞凋亡的抑制、分化的重新编程以及染色体不稳定性。这些变化可以支持将游离型HPV基因组整合至宿主细胞的染色体中,并且有助于进一步过表达病毒基因E6和E7,从而导致在***变的早期步骤期间E7癌蛋白水平的增加。
病毒癌蛋白E6和E7在癌变发生期间至关重要进一步由以下事实证明:高风险E7蛋白与高风险E6合作可以在体外有效地永生化人原代角化细胞。此外,E6和E7癌基因的一致性过表达是诱导和维持***细胞的已转化表型所需要的。
因此,E6和E7蛋白的检测似乎是优越的诊断工具。本领域已知各种抗体,但是它们表现出低敏感性或特异性,或者被描述为与各种HPV类型的E7蛋白交叉反应。而且由于多克隆抗体只能由一种动物以有限的量产生,因此存在批次间差异。产生针对E7蛋白的高度特异性和敏感性的单克隆抗体的困难主要是由于E7蛋白的低免疫原性。
因此,本发明的一个目的是克服上述困难并提供高度特异性且更灵敏的方法用于HPV感染的有成本效益的、快速且可靠的诊断,例如经由检测早期HPV蛋白(诸如E5、E6或E7)的存在或不存在。
虽然目前可获得针对两种最常见的高风险HPV的有效预防性疫苗,但是高成本、社会认可问题以及通过其可以提供疫苗的卫生保健***的局限性将很可能限制这种疫苗对女性的可用性,特别是在最常发现HPV相关的***与生殖器癌的发展中国家的女性。因此,仍然需要确定直接治疗以靶向HPV感染和源于HPV感染的癌症(诸如***)。因此,本发明寻求解决的另一个技术问题是提供有效且高亲合力的基于T细胞受体的分子,其可用于治疗和预防HPV介导的疾病的治疗方法。
在第一方面,上述问题被通过包含与选自SEQ ID No.9至28的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%序列同一性的抗原识别构建体解决。
如本申请的实施例部分(实施例1至9)的表格中所示,SEQ ID No 9至28对应于TCRT1至T9的CDR3区。出人意料地发现,与针对HPV抗原的现有技术的TCR状态相比,本发明的HPV应答性TCR是高度亲合的。在一些情况下,与现有技术的TCR的状态相比,本发明的TCR更有特异性、更敏感、更具选择性和/或更具亲合性。在本发明的一优选的实施方案中,抗原识别构建体包含与选自SEQ ID No.9至28的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%序列同一性的互补决定区3(CDR3)。
本发明的抗原识别构建体的CDR3可以被突变。SEQ ID NO:9至28的CDR3序列的突变优选地包括不超过三个、优选两个且最优选不超过一个氨基酸残基的取代、缺失、添加或***。
在另一另外的或可替代的实施方案中,抗原识别构建体是HPV抗原识别构建体。
在另一另外的或可替代的实施方案中,抗原识别构建体还可包含CDR1和CDR2结构域序列。在可变结构域内,CDR1和CDR2存在于多肽链的可变(V)区中,并且CDR3包括一些V区、所有多样性(D)区和连结(J)区。CDR3是最可变的,并且是负责识别抗原的主要CDR。CDR1和CDR2序列可以被选自人可变链等位基因的CDR序列。
天然αβ异二聚体TCR具有α链和β链。每条链包含可变区、连接区和恒定区,并且β链还通常在可变区和连接区之间含有短的多样性区,但是这个多样性区通常被认为是连接区的一部分。每个可变区包含被嵌入在框架序列中的三个CDR(互补决定区),一个是名为CDR3的高变区。有由它们的框架序列、CDR1序列和CDR2序列以及由部分限定的CDR3序列区分开的若干种类型的α链可变(Vα)区和若干种类型的β链可变(Vβ)区。Vα类型在IMGT命名中由唯一的TRAV编号表示,Vβ类型由唯一的TRBV编号表示。
因此,在一另外的或可替代的实施方案中,本发明的抗原识别构建体包含如实施例部分的表格所提供的组合中的CDR1、CDR2和CDR3序列,所述实施例部分的表格显示各自的可变链等位基因连同CDR3序列。因此,优选的是包含至少一个、优选所有三个CDR序列CDR1、CDR2和CDR3的本发明的抗原识别构建体。
在本发明的一实施方案中,抗原识别构建体特异性结合人***瘤病毒(HPV)抗原;优选地,其中HPV抗原是选自以下的蛋白:HPV 16 E5、HPV 16 E6、HPV 16 E7、HPV 18 E6和HPV 18 E7。
如本文所用的术语“特异性”或“抗原特异性”或“特异性的针对”给定抗原意思是抗原识别构建体可以特异性地结合所述抗原,优选HPV抗原,更优选具有高亲合力。例如,如果表达TCR的T细胞一经与用低浓度的HPV抗原(诸如下文提供的HPV 16 E5、E6和E7抗原)(例如,约10-11mol/l、10-10mol/l、10-9mol/l、10-8mol/l、10-7mol/l、10-6mol/l、10-5mol/l)脉冲的靶细胞共培养就分泌至少约200pg/ml或更多(例如250pg/ml或更多、300pg/ml或更多、400pg/ml或更多、500pg/ml或更多、600pg/ml或更多、700pg/ml或更多、1000pgml或更多、2,000pg/ml或更多、2,500pg/ml或更多、5,000pg/ml或更多)的干扰素γ(IFN-γ),则TCR可以被认为对HPV抗原具有“抗原特异性”。可替代地或另外地,如果表达TCR的T细胞一经与用低浓度的HPV抗原脉冲的靶细胞共培养就分泌是未转导背景水平的IFN-γ的至少两倍的IFN-γ,则TCR可以被认为对HPV具有“抗原特异性”。可以–例如–用ELISA分析如上所述的此类“特异性”。
在本发明的一可替代的或另外的实施方案中,抗原识别构建体选择性结合人***瘤病毒(HPV)抗原;优选地,其中HPV抗原是选自以下的蛋白:HPV 16 E5、HPV 16 E6、HPV 16E7、HPV 18 E6和HPV 18 E7。
术语“选择性”或“选择性识别/结合”被理解为是指抗体或T-细胞受体选择性识别或结合优选仅一个特异性表位并且优选地不显示或基本上不显示与另一个表位的交叉反应性的性质。优选地,“选择性”或“选择性识别/结合”意思是抗原识别构建体(例如TCR)选择性识别或结合优选仅一个特异性表位,并且优选地不显示或基本上不显示与另一个表位的交叉反应性,其中所述表位对于一种蛋白质是唯一的,使得抗原识别构建体不显示或基本上不显示与另一个表位和另一种蛋白质的交叉反应性。
根据本发明的抗原识别构建体优选地选自抗体或其衍生物或片段,或T细胞受体(TCR)或其衍生物或片段。本发明的抗体或TCR的衍生物或片段应优选地保留亲体分子的抗原结合/识别能力,特别是如上所解释的其特异性和/或选择性。
在本发明的一实施方案中,本发明的TCR能够以主要组织相容性复合体(MHC)I类依赖性方式识别HPV抗原。如本文所用的“MHC I类依赖性方式”意思是在MHC I类分子的背景中TCR一经结合HPV抗原就引起免疫应答。MHC I类分子可以是本领域已知的任何MHC I类分子,例如HLA-A分子。在本发明的优选的实施方案中,MHC I类分子是HLA-A2分子,优选HLAA2.01型。
将以下表位(SEQ ID NO:1至9)用于产生实施例的TCR:YIIFVYIPL(HPV 16E563-71)、KLPQLCTEL(HPV 16 E611-19)、TIHDIILECV(HPV 16 E629-38)、YMLDLQPET(HPV 16E711-19)、YMLDLQPETT(HPV 16 E711-20)、TLGIVCPI(HPV 16 E786-93)、KCIDFYSRI(HPV 18E667-75)、FQQLFLNTL(HPV 18 E786-94)。因此,本发明的一实施方案描述了对于以上HPV表位之一是特异性的和/或选择性的抗原识别构建体。技术人员知道,取决于哪个CDR3存在,本发明的抗原识别构建体如实施例部分中公开的那样特异性地和/或选择性地结合其各自的表位。
本发明提供了单链抗原识别构建体和双链识别构建体两者。
本发明特别提供了TCR作为抗原识别构建体或其片段或衍生物。TCR优选地是人的,其被理解为从人TCR基因座产生并因此包含人TCR序列。此外,本发明的TCR的特征可以在于它是人类起源的并且特异性识别HPV抗原。在这方面术语“起源”是指来源于各自“原始的”序列但是含有氨基酸改变的经突变的序列。例如,人类起源的TCR可以包含被人工引入到人TCR序列中的非人物种的TCR序列。
本发明的另一实施方案另外地或可替代地提供诱导免疫应答的上述抗原识别构建体,优选地其中免疫应答的特征在于干扰素(IFN)γ水平的增加。
可以提供本发明的TCR作为单链α或β分子,或者可替代地可作为由α和β链两者或γ和δ链两者组成的双链构建体。因此,本发明的TCR优选地在其α链中包含与选自SEQ IDNo.9、10、12、14、16、18、21、23、25、27的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%序列同一性的CDR3,和/或在其β链中包含与选自SEQ ID No.11、13、15、17、19、20、22、24、26、28的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%序列同一性的CDR3。
优选地,双链TCR或其抗原结合片段在第一多肽链中包含根据SEQ ID NO:9的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:11的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:10的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:11的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:12的氨基酸序列和在第二多肽链中包含根据SEQ IDNO:13的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:14的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:15的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:16的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:17的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:18的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:19的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:18的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:20的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:21的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:22的氨基酸序列;或在第一多肽链中的根据SEQ ID NO:23的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:24的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:25的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:26的氨基酸序列;或在第一多肽链中包含根据SEQ ID NO:27的氨基酸序列和在第二多肽链中包含根据SEQ ID NO:28的氨基酸序列。上述双链TCR或其抗原结合片段中的任一个是本发明的优选的TCR。在一些实施方案中,本发明的双链TCR的CDR3可以被突变。如上所提供的SEQ IDNO:9至28的CDR3序列的突变优选地包括不超过三个、优选两个并且最优选不超过一个氨基酸残基的取代、缺失、添加或***。在一些实施方案中,第一多肽链可以是TCRα或γ链,并且第二多肽链可以是TCR β或δ链。优选的是αβ或γδTCR的组合。
TCR或其抗原结合片段由TCR α链与TCR β链,或γ与δ链组成。此类双链TCR在每条链内包含含有CDR1、CDR2和CDR3序列的可变区。TCR包含CDR1至CDR3序列,所述CDR1至CDR3序列包含于以下中所示的可变链氨基酸序列中:SEQ ID NO:29和SEQ ID NO:31(T1a);或SEQ ID NO:30和SEQ ID NO:31(T1b);或SEQ ID NO:32和SEQ ID NO:33(T2);或SEQ ID NO:34和SEQ ID NO:35(T3);或SEQ ID NO:36和SEQ ID NO:37(T4);或SEQ ID NO:38和SEQ IDNO:39(T5a);或SEQ ID NO:38和SEQ ID NO:40(T5b);或SEQ ID NO:41和SEQ ID NO:42(T6);或SEQ ID NO:43和SEQ ID NO:44(T7);或SEQ ID NO:45和SEQ ID NO:46(T8);或SEQID NO:47和SEQ ID NO:48(T9)。
本发明的一些实施方案涉及由TCR α链和TCR β链组成的TCR或其片段,其中所述TCR包含分别根据以下的α和β链的可变区序列:SEQ ID NO:29和31(T1a);或30和31(T1b);或32和33(T2);或34和35(T3);或36和37(T4);或38和39(T5a);或38和40(T5b);或41和42(T6);或43和44(T7);或45和46(T8);或47和48(T9)。
本发明TCR还可包含来源于任何适合的物种(诸如,例如人或小鼠)的恒定区。在本发明的实施方案中,本发明TCR还包含人恒定区。在一些优选的实施方案中,本发明的TCR的恒定区可以被略微地修改,例如通过引入可以增加TCR稳定性的鼠科动物序列。
如本文所用,当指代抗原识别构建体或TCR或本文所述的TCR的任何组分(例如互补决定区(CDR)、可变区、恒定区、α链和/或β链)时,术语“鼠科动物”或“人类”意思是分别来源于小鼠或人的未重新排列TCR基因座的TCR(或其组分)。
在本发明的一实施方案中,嵌合TCR可以包含TCR的α链和TCR的β链。本发明的嵌合TCR的α链和β链中的每一条可以独立地包含任何氨基酸序列。优选地,α链包含如上所述的α链的人可变区和α链的鼠科动物恒定区。
在一实施方案中,本发明的TCR是包含根据以上实施方案的人可变区和人恒定区的人TCR。
可以提供本发明的TCR作为单链TCR(scTCR)。scTCR可以包括第一TCR链(例如α链)的可变区的多肽和整个(全长)第二TCR链(例如β链)的多肽,或反之亦然。此外,scTCR可以任选地包含将两个或更多个多肽连接在一起的一个或更多个接头。如本文所述,接头可以是,例如将两条单链连接在一起的肽。还提供了本发明的此类scTCR,其被融合到人细胞因子(诸如IL-2、IL-7或IL-15)。
根据本发明的抗原识别构体还可以以包含至少两个scTCR分子的多聚体复合物的形式被提供,其中所述scTCR分子各自被融合到至少一个生物素部分,并且其中所述scTCR通过生物素-链霉亲和素相互作用相互连接以允许形成所述多聚体复合物。用于产生多聚体TCR的类似方法也是可能的并且被本公开包括。还提供了更高等级的多聚体复合物,其包含多于两个的本发明的scTCR。
为了本发明的目的,TCR是具有至少一个TCR α和/或TCR β可变结构域的部分。通常它们包含TCR α可变结构域和TCR β可变结构域两者。它们可以是αβ异二聚体或可以是单链形式。为了用于过继性疗法,αβ异二聚体TCR可以例如被转染为具有胞质结构域和跨膜结构域两者的全长链。如果需要,可以存在各自恒定结构域的残基之间的引入的二硫键。
在本发明的第一方面的一另外优选的实施方案中,抗原识别构建体如上所述是TCR。TCR优选地包含至少一条α和/或β TCR链,其中所述TCR链包含根据SEQ ID No.22–39中所示的TCR链中任一条的氨基酸序列,或与SEQ ID No.22至39中所示的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%同一性的氨基酸序列。
在一优选的实施方案中,抗原识别构建体是人TCR或其片段或衍生物。人TCR或其片段或衍生物是包含超过50%的相应人TCR序列的TCR。优选地,只有一小部分的TCR序列是人工起源的或来源其它物种。然而,已知例如来自在恒定结构域中具有鼠科动物序列的人类起源的嵌合TCR是有利的。因此,特别优选的是根据本发明的TCR,其在它们的恒定结构域的细胞外部分含有鼠科动物序列。
因此,还优选的是本发明的抗原识别构建体能够以人白细胞抗原(HLA)依赖性方式,优选地以HLA-A02依赖性方式识别其抗原。在本发明的上下文中术语“HLA依赖性方式”意思是只有在抗原性肽由HLA呈递的情况下抗原识别构建体才结合抗原。
在一实施方案中,根据本发明的抗原识别构建体优选地诱导免疫应答,优选地其中免疫应答的特征在于干扰素(IFN)γ水平增加。
本发明还提供了包含本文所述的任何TCR(或其功能变体)的功能部分的多肽,例如如实施例部分提供的TCR T1至T9中的任一个的功能部分。如本文所用的术语“多肽”包括寡肽并且是指由一个或更多个肽键连接的氨基酸的单链。关于本发明的多肽,功能部分可以是包含作为TCR一部分的TCR(或其功能变体)的连续氨基酸的任何部分,条件是功能部分特异性地结合如在SEQ ID NO 1至8所公开的HPV抗原。当关于TCR(或其功能变体)使用时,术语"功能部分"是指本发明的TCR(或其功能变体)的任何部分或片段,所述部分或片段保留其作为TCR一部分的TCR(或其功能变体)(亲体TCR或其亲体功能变体)的生物活性。功能部分包含,例如保留特异性地结合HPV抗原(例如SEQ ID NO 1至8,以HLA-A2依赖性方式)或者在与亲体TCR(或其功能变体)类似程度上、相同程度上或在较高程度上检测、治疗或预防癌症的能力的TCR(或其功能变体)的那些部分。关于亲体TCR(或其功能变体),功能部分可以包含例如约10%、25%、30%、50%、68%、80%、90%、95%或更大的亲体TCR可变序列(或其功能变体)。
功能部分可以在该部分的氨基末端或羧基末端或在两个末端处包含另外的氨基酸,在亲体TCR或其功能变体的氨基酸序列中未发现所述另外的氨基酸。合乎期望的是,另外的氨基酸不干扰功能部分的生物功能,例如特异性结合HPV抗原;和/或具有检测癌症、治疗或预防癌症等的能力。更合乎期望的是,与亲体TCR或其功能变体的生物活性相比,另外的氨基酸增强了生物活性。
多肽可以包含本发明的TCR或其功能变体的α链和β链之一或两者的功能部分,诸如包含本发明的TCR或其功能变体的α链和/或β链的可变区的CDR1、CDR2和CDR3中的一个或更多个的功能部分。在本发明的实施方案中,多肽可以包含功能部分,所述功能部分包含SEQ ID NO:9至28的氨基酸序列(本发明的TCR的可变区的CDR3)或它们的组合。在本发明的实施方案中,本发明多肽可以包含例如含有以上所述的CDR区的组合的本发明的TCR或其功能变体的可变区。就这一点而言,多肽可以包含SEQ ID NO:29至48中任一个的氨基酸序列(α或β链的可变区)。
在一些情况下,本发明的构建体可以包含含有根据SEQ ID NO:9至48中任一个的序列(CDR序列或整个可变区)或其功能片段的一条或两条多肽链,并且还包含其它氨基酸序列(例如编码免疫球蛋白或其部分的氨基酸序列),则本发明的蛋白可以是融合蛋白。就这一点而言,本发明还提供了融合蛋白,其包含至少一条本文所述的本发明的多肽连同至少一条其他多肽。其他多肽可以作为融合蛋白的单独多肽存在,或者可以作为与一条本文所述的本发明的多肽一起在框架中(in frame)(一前一后地(in tandem))被表达的多肽存在。其他多肽可以编码任何肽分子或蛋白质性分子或它们的部分,包括但不限于免疫球蛋白、CD3、CD4、CD8、MHC分子、CD1分子(例如CD1a、CD1b、CDlc、CD Id等)。
融合蛋白可以包含本发明的多肽的一个或更多个拷贝和/或其他多肽的一个或更多个拷贝。例如,融合蛋白可以包含本发明多肽和/或其他多肽的1、2、3、4、5或更多个拷贝。制备融合蛋白的适合的方法是本领域已知的,并且包括例如重组方法。在本发明的一些实施方案中,本发明的TCR(及其功能部分和功能变体)、多肽和蛋白可以被表达作为包含连接α/γ链和β/δ链的接头肽的单一蛋白。就这一点而言,本发明的TCR(及其功能变体和功能部分)、多肽和蛋白包含本发明的TCR(T1至T9)的可变区的氨基酸序列,并且还可以包含接头肽。接头肽可以有利地促进宿主细胞中重组TCR(包括其功能部分和功能变体)、多肽和/或蛋白质的表达。接头肽可以包含任何适合的氨基酸序列。用于单链TCR构建体的接头序列在本领域中是众所周知的。此类单链构建体还可以包括一个或两个恒定结构域序列。一经宿主细胞表达包括接头肽的构建体,接头肽也可以被切割,从而导致分开的α和β链。
如上所提及的,可以在抗体的框架中提供本发明的TCR的结合功能。术语“抗体”以其各种语法形式在本文中用于指代免疫球蛋白分子和免疫球蛋白分子的免疫活性部分(即含有抗体结合位点或互补位的分子)。此类分子也被称为免疫球蛋白分子的"抗原结合片段"。本发明还提供了特异性结合本文所述的抗原的抗体或其抗原结合部分。抗体可以是本领域已知的任何类型的免疫球蛋白。例如,抗体可以是任何同种型的,例如IgA、IgD、IgE、IgG、IgM等。抗体可以是单克隆或多克隆的。抗体可以是天然存在的抗体,例如从哺乳动物(例如小鼠、兔、山羊、马、鸡、仓鼠、人等)分离和/或纯化的抗体。可替代地,抗体可以是经基因工程化的抗体,例如人源化抗体或嵌合抗体。抗体可以是单体形式或聚合体形式。
本发明还提供了本文所述的任何抗体的抗原结合部分。抗原结合部分可以是具有至少一个抗原结合位点的任何部分,诸如Fab、F(ab')2、dsFv、sFv、双抗体和三抗体。可以使用常规重组DNA技术方法产生单链可变区片段(sFv)抗体片段,其由包含经由合成肽连接至轻抗体链的V结构域的抗体重链的可变(V)结构域的截短的Fab片段组成。类似地,可以通过重组DNA技术制备二硫化物-稳定化的可变区片段(dsFv),然而本发明的抗体片段不限于这些示例性类型的抗体片段。此外,抗体或其抗原结合部分可以被修饰以包含可检测的标记,诸如例如放射性同位素、荧光团(例如异硫氰酸荧光素(FITC)、藻红蛋白(PE))、酶(例如碱性磷酸酶、辣根过氧化物酶)和元素颗粒(例如金颗粒)。在一些情况下,与SEQ ID NO9至28中提供的CDR3序列相比,TCR CDR3序列可以被略微修饰,但优选地不超过3个氨基酸残基、优选地仅两个并且最优选地仅一个氨基酸位置。优选地,抗体包含CDR3、优选如针对在本公开的实施例部分中的TCR T1至T9所示的组合中的所有CDR1至CDR3区。
制备抗体的适合的方法是本领域已知的。例如,标准杂交瘤方法被描述于例如Kohler和Milstein,Eur.J.Immunol,5,51 1-519(1976),Harlow和Lane(编辑),Antibodies:A Laboratory Manual,CSH Press(1988),和C.A.Janeway等人(编辑),Immunobiology,第8版,Garland Publishing,New York,NY(201 1))中。可替代地,其他方法诸如EBV杂交瘤方法(Haskard和Archer,J.Immunol.Methods,74(2),361-67(1984),和Roder等人,Methods Enzymol,121,140-67(1986))和噬菌体载体表达***(参见,例如Huse等人.,Science,246,1275-81(1989))是本领域已知的。此外,在非人类动物中产生抗体的方法描述于例如美国专利5,545,806、5,569,825和5,714,352以及美国专利申请公开第2002/0197266号Al中。
本发明的一些实施方案还涉及TCR或其功能片段和多肽,它们是可溶性TCR。如本文所用的,术语“可溶性T细胞受体”是指天然TCR的异二聚体截短变体,其包含通过二硫键连接的TCR α-链和β-链的细胞外部分,但是其缺乏天然蛋白的跨膜和胞质结构域。术语"可溶性T细胞受体α链序列和可溶性T细胞受体β链序列"是指缺乏跨膜结构域和胞质结构域的TCR α链和β链序列。可溶性TCR α链和β链的序列(氨基酸或核酸)可以与天然TCR中相应的序列相同,或者与相应的天然TCR序列相比可以包含变体可溶性TCR α链和β链序列。如本文所用的术语“可溶性T细胞受体”包含具有变体或非变体可溶性TCR α链和β链序列的可溶性TCR。变异可以在可溶性TCR α链和β链序列的可变区或恒定区中,并且可以包括但不限于氨基酸缺失突变、***突变、取代突变以及不改变氨基酸序列的核酸序列变化。在任何情况下,本发明的可溶性TCR保留它们亲体分子的结合功能。
通过编码本发明的抗原识别构建体或任何上述蛋白或多肽构建体的核酸进一步解决以上问题。核酸优选地(a)具有编码根据本发明的抗原识别构体的链;(b)具有与(a)中的链互补的链;或(c)具有在严格条件下与(a)或(b)中所述的分子杂交的链。严格条件是本领域技术人员已知的,具体来自Sambrook等人,“分子克隆(Molecular Cloning)”。除此之外,核酸任选地具有另外的序列,其对于表达对应于蛋白的核酸序列,特别是对于在哺乳动物/人细胞中表达)是必需的。所使用的核酸可以被包含在适用于允许在细胞中表达与肽对应的核酸序列的载体中。然而,也可以将核酸用于转化呈递细胞,其不应该被限制于经典抗原呈递细胞(诸如树突细胞),以这样的方式它们自己在其细胞表面上产生相应的蛋白。
如本文所用的“核酸”包括“多核苷酸”、“寡核苷酸”和“核酸分子”并且通常意思是DNA或RNA的聚合物,其可以是单链的或双链的、合成的或从天然来源获得的(例如分离的和/或纯化的),其可以包含天然的、非天然的或改变的核苷酸,并且其可以含有天然的、非天然的或改变的核苷酸间键(诸如氨基磷酸酯键或硫代磷酸酯键)而不是在未修饰的寡核苷酸的核苷酸之间发现的磷酸二酯。
优选地,本发明的核酸是重组的。如本文所用的,术语“重组”是指(i)通过将天然或合成的核酸片段连接至可以在活细胞中复制的核酸分子而在活细胞外构建的分子,或(ii)由在上面(i)中所述的那些的复制产生的分子。为了本文的目的,复制可以是体外复制或体内复制。核酸可以包含编码本文所述的任何TCR、多肽或蛋白质或者它们的功能部分或功能变体的任何核苷酸序列。
此外,本发明提供了包含如上所述的根据本发明的核酸的载体。合乎期望的是,载体是表达载体或重组表达载体。术语“重组表达载体”在本发明的上下文中指允许在适合的宿主细胞中表达mRNA、蛋白质或多肽的核酸构建体。本发明的重组表达载体可以是任何适合的重组表达载体,并且可以被用于转化或转染任何适合的宿主。适合的载体包括那些被设计用于繁殖和扩增或用于表达或用于两者的载体,诸如质粒和病毒。动物表达载体的实例包括pMP71、pEUK-Cl、pMAM、pMAMneo和pSB100Xo。优选地,重组表达载体是病毒载体(例如逆转录病毒载体)或非病毒载体(例如基于转座子的睡美人载体(Sleeping Beautyvector))。重组表达载体包含调控序列(诸如转录和翻译起始与终止密码子),其对载体将被引入其中并且在其中应进行本发明的核酸的表达的宿主细胞(例如,细菌、真菌、植物或动物)的类型是特异性的。此外,本发明的载体可以包括一个或更多个标记基因,其允许转化或转染的宿主的选择。重组表达载体可以包含天然或规范的启动子,所述启动子与编码本发明的构建体的核苷酸序列或与编码本发明的构建体的核苷酸序列互补或杂交的核苷酸序列可操作地连接。启动子的选择包括例如强启动子、弱启动子、诱导型启动子、组织特异性启动子和发育特异性启动子。启动子可以是非病毒启动子或病毒启动子。本发明的重组表达载体可以被设计用于瞬时表达、稳定表达或两者。此外,可以制备重组表达载体以用于组成型表达或用于诱导型表达。
本发明还涉及包含根据本发明的抗原识别构建体的宿主细胞。特别地,本发明的宿主细胞包含如上文所述的核酸或载体。宿主细胞可以是真核细胞(例如植物、动物、真菌或藻类),或者可以是原核细胞(例如细菌或原生动物)。宿主细胞可以是培养的细胞或原代细胞(即直接从生物体(例如人)分离)。宿主细胞可以是粘附细胞或悬浮细胞(即悬浮生长的细胞)。为了产生重组TCR、多肽或蛋白质的目的,宿主细胞优选是哺乳动物细胞。最优选地,宿主细胞是人细胞。虽然宿主细胞可以是任何细胞类型,可以来源于任何类型的组织,并且可以是任何发育阶段,但是宿主细胞优选是外周血白细胞(PBL)或外周血单个核细胞(PBMC)。更优选地,宿主细胞是T细胞。T细胞可以是任何T细胞,诸如培养的T细胞,例如原代T细胞,或来自培养的T细胞系(例如Jurkat、SupT1等)的T细胞,或从哺乳动物获得的T细胞,优选地来自人患者的T细胞或T细胞前体。如果从哺乳动物获得,可以从多种来源获得T细胞,所述来源包括但不限于血液、骨髓、***、胸腺或其它组织或流体。还可以富集或纯化T细胞。优选地,T细胞是人T细胞。更优选地,T细胞是从人分离的T细胞。T细胞可以是任何类型的T细胞并且可以是任何发育阶段的,包括但不限于CD4阳性和/或CD8阳性、CD4阳性辅助T细胞(例如Th1和Th2细胞)、CD8阳性T细胞(例如细胞毒性T细胞)、肿瘤浸润细胞(TIL)、记忆T细胞、天然T细胞等。优选地,T细胞是CD8阳性T细胞或CD4阳性T细胞。
优选地,本发明的宿主细胞是淋巴细胞,优选T淋巴细胞,诸如CD4或CD8阳性T细胞。此外宿主细胞优选是特异性针对表达MAGE-A1的肿瘤细胞的肿瘤反应性T细胞。
本发明的一另外的方面涉及本文所公开的抗原识别构建体、核酸、载体和/或宿主细胞用于医药中的用途。在一优选实施方案中的在医药中的用途包括在诊断、预防和/或治疗传染性疾病(优选HPV感染)或增殖性疾病(诸如恶性或良性肿瘤疾病)中的用途。肿瘤疾病是例如HPV相关的癌症。
本发明的构建体、蛋白质、TCR抗体、多肽和核酸特别用于免疫疗法,优选用于过继性T细胞疗法。本发明的化合物的施用可以例如涉及将本发明的T细胞输注至所述患者中。优选地,此类T细胞是患者的自体T细胞,其是用本发明的核酸或抗原识别构建体体外转导的。
还通过用于制备表达HPV特异性抗原识别构建体(ARC)的细胞系的方法来解决本发明的目的,该方法包括:
a.提供适合的宿主细胞,
b.提供编码ARC的基因构建体,其中所述ARC包含具有这样的氨基酸序列的CDR3,所述氨基酸序列与选自SEQ ID No.9至28的氨基酸序列具有至少50%、60%、70%、80%、90%、95%、98%、99%或100%的序列同一性,
c.将所述基因构建体引入所述适合的宿主细胞中,
d.由所述适合的宿主细胞表达所述基因构建体。
在一优选实施方案中,以上方法还可以包括包括所述ARC的细胞表面呈现的步骤。
当然,还优选的是本发明的这个方面的上下文,所述ARC是根据如上文所述的本发明的方面的ARC。在这方面,还另外地或可替代地优选的是,所述ARC是哺乳动物起源的,优选人类起源的。
用于本发明的方法的优选适合的宿主细胞是哺乳动物细胞,特别是人细胞,诸如人T细胞。上文详细描述了用于本发明的T细胞。
根据本发明的方法产生的ARC在一实施方案中是TCR。例如,也包括具有另外的(功能的)结构域的TCR或提供有可替代的结构域的TCR,例如提供有外来跨膜结构域作为膜锚着点的TCR。根据本发明产生的TCR是例如α/βTCR、γ/δTCR或单链TCR(scTCR)。此外,本发明包括的TCR形式通常是本领域已知的任何TCR,特别是上文所述的那些。
合乎需要的是,用于根据本发明的方法中的转染***是逆转录病毒载体***。此类***是本领域技术人员所熟知的。
在一实施方案中,本发明还包括从细胞中纯化ARC以及任选地在T-细胞中重组翻译的ARC片段的另外的方法步骤。
在本发明的可替代的方面,提供了通过用于产生T细胞受体(TCR)的方法获得或可获得的T细胞,所述T细胞受体(TCR)特异性针对肿瘤细胞并且具有如上文所述的高亲合力。此类T细胞取决于在本发明的方法中使用的宿主细胞,例如人或非人T细胞,优选人TCR。
本发明的TCR、多肽、蛋白质、(包括它们的功能变体)、核酸、重组表体载体、宿主细胞(包括其群体)和抗体(包括其抗原结合部分)可以是分离的和/或纯化的。如本文所用的术语"分离的"意思是已经从其天然环境中移除。如本文所用的术语"纯化的"意思是已经提高了纯度,其中"纯度"是相对术语并且不必被解释为绝对纯度。例如,纯度可以是至少约50%,可以是大于60%、70%、80%、90%、95%,或可以是100%。
本发明的抗原识别构建体、TCR、多肽、蛋白质(包括它们的功能变体)、核酸、重组表达载体、宿主细胞(包括其群体)和抗体(包括其抗原结合部分)(其全部在下文中被统称为"本发明的TCR材料")可以被配制成组合物,诸如药物组合物。在这方面,本发明提供了包含本文所述的任何TCR、多肽、蛋白质、功能部分、功能变体、核酸、表达载体、宿主细胞(包括其群体)和抗体(包括其抗原结合部分)和药学上可接受的载体的药物组合物。含有任何本发明的TCR材料的本发明的药物组合物可以包含超过一种本发明的TCR材料(例如多肽和核酸),或者两种或更多种不同的TCR(包括它们的功能部分和功能变体)。可替代地,药物组合物可以包含本发明的TCR材料与另一种药学活性剂或药物(诸如化学治疗剂,例如天冬酰胺酶、白消安、卡铂、顺铂、道诺霉素、阿霉素、氟尿嘧啶、吉西他滨、羟基脲、甲氨蝶呤、紫杉醇、利妥昔单抗、长春碱、长春新碱等)的组合。优选地,载体是药学上可接受的载体。关于药物组合物,载体可以是通常用于所考虑的特定的本发明TCR材料的那些载体中的任一种。此类药学上可接受的载体对于本领域技术人员来说是公知的,并且公众可容易获得。优选的是药学上可接受的载体为在使用条件下不具有有害副作用或毒性的载体。
因此,还提供了药物组合物,其包含本发明的本文所述的任何产物,特别是任何蛋白质、核酸或宿主细胞。在优选的实施方案中,药物组合物用于免疫疗法。
优选地,通过注射(例如静脉注射地)施用本发明TCR材料。当本发明的TCR材料是表达本发明的TCR(或其功能变体)的宿主细胞时,用于注射用细胞的药学上可接受的载体可以包括任何等渗载体,诸如,例如生理盐水(约0.90%w/v的NaCl水溶液、约300mOsm/LNaCl水溶液或每升水约9.0g NaCl),NORMOSOL R电解质溶液(Abbott,Chicago,IL),PLASMA-LYTE A(Baxter,Deerfield,IL),约5%葡萄糖水溶液或乳酸林格氏液(Ringer'slactate)。在实施方案中,药学上可接受的载体补充有人血清蛋白。
为了本发明的目的,施用的本发明的TCR材料的量或剂量(例如,当本发明的TCR材料是一个或更多个细胞时的细胞数量)应该足以在对象或动物中经合理的时间范围实现例如治疗性或预防性应答。例如,在从施用时间开始的从约2小时或更长时间(例如12至24或更多小时)的时间段内,本发明的TCR材料的剂量应该足以与癌症抗原结合或检测、治疗或预防癌症。在某些实施方案中,时间段可能甚至更长。将通过特定的本发明TCR材料的功效和动物(例如人)的状况以及待治疗的动物(例如人)的体重来确定剂量。
预期可以将本发明药物组合物、TCR(包括其功能变体)、多肽、蛋白质、核酸、重组表达载体、宿主细胞或细胞群用于治疗或预防癌症、HPV感染或HPV阳性初癌的方法中。不受特定理论的束缚,本发明的TCR(和其功能变体)据信特异性地结合HPV抗原,使得TCR(或其相关的本发明多肽或蛋白质及它们的功能变体)当由细胞表达时能够介导针对表达本发明的HPV抗原的靶细胞的免疫应答。就这一点而言,本发明提供了治疗或预防哺乳动物体中的病况的方法,其包括以有效治疗或预防哺乳动物中的病况的量向哺乳动物施用本文所述的任何药物组合物、TCR(和其功能变体)、多肽或蛋白质,包含编码本文所述的任何TCR(和其功能变体)、多肽、蛋白质的核苷酸序列的任何核酸或重组表达载体,或包含编码本文所述的任何TCR(和其功能变体)、多肽或蛋白质的重组载体的任何宿主细胞或细胞群,其中所述病况是癌症、HPV感染或HPV阳性初癌。
可用于本发明中的药学上可接受的载体或稀释剂的实例包括稳定剂诸如SPGA、碳水化物(例如山梨糖醇、甘露糖醇、淀粉、蔗糖、葡萄糖、葡聚糖)、蛋白质(诸如白蛋白或酪蛋白)、含有蛋白质的试剂(诸如牛血清或脱脂乳)和缓冲剂(例如磷酸盐缓冲剂)。
如本文所用的,术语"治疗"和"预防"以及由此产生的词语,不一定意味着100%或完全的治疗或预防。相反,存在本领域普通技术人员认识到具有潜在的益处或治疗效果的不同程度的治疗或预防。在这方面,本发明的方法可以提供任何量的任何水平的对哺乳动物中病况的治疗或预防。此外,由本发明方法提供的治疗或预防可以包括治疗或预防一种或更多种病况或病况的症状,例如正在治疗或预防的癌症。例如,治疗或预防可以包括促进肿瘤的消退。此外,为了本文的目的,"预防"可以包含延迟病况或其症状或状况的发作。
还提供了检测哺乳动物中病况存在的方法。该方法包括(i)将包含来自哺乳动物的一种或更多种细胞的样品与本文所述的本发明的TCR(和其功能变体)、多肽、蛋白质、核酸、重组表达载体、宿主细胞、细胞群、抗体或其抗原结合部分或药物组合物中的任一种接触,从而形成复合物,并且检测复合物,其中复合物的检测指示在哺乳动物体中病况的存在,其中所述病况是癌症、HPV 16感染或HPV阳性初癌。
关于检测哺乳动物中病况的本发明方法,细胞样品可以是包含全细胞、其裂解物或全细胞裂解物的级分(如核或细胞质级分、全蛋白级分或核酸级分)的样品。
为了本发明检测方法的目的,关于哺乳动物,接触可以体外或体内发生。优选地,接触在体外。
此外,复合物的检测可以通过本领域已知的许多方法进行。例如,本文所述的本发明的TCR(和其功能变体)、多肽、蛋白质、核酸、重组表达载体、宿主细胞、细胞群、或抗体或其抗原结合部分可以被用可检测标记(诸如,例如,放射性同位素、荧光团(如异硫氰酸荧光素(FITC)、藻红蛋白(PE))、酶(如碱性磷酸酶、辣根过氧化物酶)和元素颗粒(如金颗粒))标记。
为了本发明方法的目的,其中施用宿主细胞或细胞群,细胞可以是哺乳动物同种异体或自体的细胞。优选地,细胞对于哺乳动物是自体的。
关于本发明的TCR材料的上述医药应用,待治疗和/或诊断的癌症可以是任何癌症,包括以下中的任一种:急性淋巴细胞性癌、急性骨髓性白血病、腺泡状横纹肌肉瘤、骨癌、脑癌、乳腺癌,***癌、肛管癌或***直肠癌,眼部的癌症、肝内胆管癌、关节癌,颈部的癌症、胆囊癌或胸膜癌,鼻部的癌症、鼻腔癌或中耳癌,口腔癌、***癌、外阴癌、慢性淋巴细胞性白血病、慢性骨髓性癌、结肠癌、食道癌、***、胃肠类癌肿瘤、神经胶质瘤、霍奇金淋巴瘤(Hodgkin lymphoma)、下咽癌、肾脏癌、喉癌、肝癌、肺癌、恶性间皮瘤、黑素瘤、多发性骨髓瘤、鼻咽癌、非霍奇金淋巴瘤(non-Hodgkin lymphoma)、口咽癌、卵巢癌、***癌、胰腺癌,腹膜癌、网膜癌和肠系膜癌,咽癌、***癌、直肠癌、肾癌、皮肤癌、小肠癌、软组织癌、胃癌、睾丸癌、甲状腺癌、子宫癌、输尿管癌和尿膀胱癌。优选的癌症是子***、口咽癌、***癌、肛管癌、***直肠癌、***癌、外阴癌或***癌。特别优选的癌症是HPV阳性癌症,诸如HPV 16或HPV 18阳性癌症。虽然最常见的与HPV 16/18感染相关的癌症包括子***、口咽癌、***癌、肛管癌、***直肠癌、***癌、外阴癌和***癌,但可以将本发明的方法用于治疗任何HPV阳性癌症,包括在其它解剖区域发生的那些癌症。
通常,本发明提供了用于治疗患有肿瘤或肿瘤疾病的对象的方法,其包括施用如本发明公开的抗原识别构建体、核酸、载体和/或宿主细胞。优选地,对象是需要此类治疗的对象。在优选实施方案中,对象是患有HPV阳性的肿瘤或肿瘤疾病的哺乳动物对象,优选人类患者。
现在将参照附图和所附序列,在以下的实施例中进一步描述本发明,但是不限于此。为了本发明的目的,如本文引用的所有参考文献通过引用整体并入。在附图和序列中:
图1:显示了在ABabDII小鼠中针对HLA-A*02.01限制性HPV16 E6表位TIHDIILECV的特异性CD8+T细胞应答的实例。将ABabDII小鼠用表达E6/7的腺病毒i.p.免疫,然后是通过s.c.施用在IFA中乳化的50μg的E6肽连同50μg的CpG ODN 1826,或者仅用肽/CpG/IFA混合物i.p.免疫。每次增强后7天通过细胞内IFNγ染色评估被免疫的动物的外周血中HPV特异性CD8+ T细胞的存在。将用豆蔻酸乙酸佛波醇酯(phorbol myristate acetate,PMA)和离子霉素刺激用作阳性对照(+ctrl)。
图2:显示了在ABabDII小鼠中针对HLA-A201限制性HPV16 E7表位TLGIVCPI的特异性CD8+ T细胞应答的实例。将ABabDII小鼠用在IFA中乳化的50μg的E7肽连同50μg的CpGODN 1826在尾巴根部s.c.免疫。每次增强后7天通过细胞内IFNγ染色评估被免疫的动物的外周血中HPV特异性CD8+ T细胞的存在。将用豆蔻酸乙酸佛波醇酯(PMA)和离子霉素刺激用作阳性对照(+ctrl)。
图3:显示了针对HLA-A*02.01限制性HPV16 E5、E6和E7表位的特异性CD8+ T细胞的FACSort策略(IFNγ捕获测定)。将来自应答小鼠的脾细胞耗竭CD4+ T细胞,并用10-8mol的各自的肽再刺激10天。对于5`RACE PCR,使用IFNγ捕获测定将HPV特异性CD8+ T细胞直接分选到RNA纯化缓冲液中。
图4:显示了新鲜制备的人PBL的HPV16 E6和E7 TCR转导。在存在200U/ml重组人白介素2的情况下,用抗CD3和抗CD28包被的板刺激1x106个新鲜分离的或冷冻的hPBMC。在刺激后48和72小时通过以下步骤进行转导:通过添加含有逆转录病毒的上清液和硫酸鱼精蛋白,接着进行旋转温育(spinoculation)(第1转导)或预加载病毒到纤维连接蛋白(Takara)包被的板上并进行旋转温育(第2转导)。通过用抗CD8和抗小鼠恒定TCRβ mAb染色评估转导功效。
图5:显示了TCR转导的人PBMC的HPV16 E6/E7肽特异性IFN-γ释放;5859 TCR对应于Seq ID No:34&35,5843B14 TCR对应于Seq ID No:36&37,14800 TCR对应于Seq ID NO:43&44。在1x104个TCR转导的T细胞与1x104个肽负载的T2细胞共培养16小时后,通过酶联免疫吸附测定法测量IFNγ产生。将用豆蔻酸乙酸佛波醇酯(PMA)和离子霉素刺激用作阳性对照(最大值);ut=未转导的PBMC。
图6:显示了在被滴定的E6特异性肽和CASKI细胞系上的TCR转导的人PBMC的HPV16E6 IFN-γ释放。左图显示了SEQ ID NO 14/15(T3)的TCR,右图显示了SEQ ID NO 16/17(T4)的TCR。在1x104个TCR转导的T细胞与1x104个肽负载的T2细胞或1x104个CASKI细胞系细胞共培养16小时后,通过酶联免疫吸附测定法测量IFNγ产生。将用豆蔻酸乙酸佛波醇酯(PMA)和离子霉素的刺激用作阳性对照(P+I)。对于HLA转导的***细胞系SiHa细胞系和头颈癌细胞系SCC-090和SCC-152(未显示),也观察到与CASKI细胞识别相当的IFNγ释放。
图7:显示了新鲜制备的人PBL的HPV16E5转导和TCR转导的人PBMC的HPV16 E5肽特异性IFN-γ释放。使用的TCR是SEQ ID NO 12/13(T2)的TCR。在存在200U/ml重组人白介素2的情况下,用抗CD3和抗CD28包被的板刺激1x106个新鲜分离的或冷冻的hPBMC。在刺激后48和72小时通过以下步骤进行转导:通过添加含有逆转录病毒的上清液和硫酸鱼精蛋白,接着进行旋转温育(第1转导)或预加载病毒到纤维连接蛋白(Takara)包被的板上并进行旋转温育(第2转导)。通过用抗CD8和抗小鼠恒定TCRβ mAb染色评估转导功效。在1x104个TCR转导的T细胞与1x104个肽负载的T2细胞共培养16小时后,通过酶联免疫吸附测定法测量IFNγ产生。将用豆蔻酸乙酸佛波醇酯(PMA)和离子霉素刺激用作阳性对照(P+I)。
SEQ ID No 1至8:显示了被本发明的TCR结合的HPV 16和18表位。
SEQ ID No 9至28:显示了本发明的TCR的α链和β链的CDR3序列。
SEQ ID No 29至48:显示了本发明的TCR的α链和β链的完整可变序列。
实施例
用于免疫动物的HPV表位:
在ABabDII小鼠中具有CTL反应性的肽表位
实施例1:识别HPV 16-E5表位YIIFVYIPL的T细胞受体T1
CDR1序列是粗体的
CDR3序列是加下划线的
全长可变链序列(CDR3序列是加下划线的):
TRAV13-1*01-CAASSYNQGGKLIF-TRAJ23*01(SEQ ID NO:29)
MTSIRAVF IFLWLQLDLV NGENVEQHPS TLSVQEGDSA VIKCTYSDSA SNYFPWYKQELGKGPQLIIDKKD QRIAVTLNKT AKHFSLHITE TQPEDSAVYF CAASSYNQGG KLIFGQGTELSVKPN
TRAV26-2*01-CILRDVNAGGTSYGKLTF-TRAJ52*01(SEQ ID NO:30)
MKLVTSIT VLLSLGIMGD AKTTQPNSME
SNEEEPVHLP CNHSTISGTD YIHWYRQLPS QGPEYVIHVNNRMAS LAIAEDRKSSTLILHRATLR DAAVYYCILR DVNAGGTSYG KLTFGQGTIL TVHPN
TRBV12-3*01-CASSLLSSYNEQFF-TRBD2*01-TRBJ2-3*01(SEQ ID NO:31)
MDSWTF CCVSLCILVA KHTDAGVIQS PRHEVTEMGQ EVTLRCKPIS GHNSLFWYRQTMMRGLELLI YIDD SGMPEDRFSA KMPNASFSTL KIQPSEPRDS AVYFCASSLL SSYNEQFFGP GTRLTVL
实施例2:识别HPV 16-E5表位YIIFVYIPL的T细胞受体T2
全长可变链序列(CDR3序列是加下划线的):
TRAV12-2*02-CAVNVDFNKFYF-TRAJ21*01(SEQ ID NO):32:
MMKSLRVLLV ILWLQLSWVW SQQKEVEQNS GPLSVPEGAI ASLNCTYSDR GSQSFFWYRQYSGKSPELIM SKED GRFTAQLNKA SQYVSLLIRD SQPSDSATYL CAVNVDFNKF YFGSGTKLNV KPN
TRBV4-1*01-CASSQDWNNEQFF-TRBD1*01-TRBJ2-1*01 SEQ ID NO:33:
MGCRLL CCAVLCLLGA VPIDTEVTQT PKHLVMGMTN KKSLKCEQHM GHRAMYWYKQKAKKPPELMF VSIN ESVPSRFSPE CPNSSLLNLH LHALQPEDSA LYLCASSQDW NNEQFFGPGT RLTVL
实施例3:识别HPV 16-E6表位TIHDIILECV的T细胞受体T3
全长可变链序列(CDR3序列是加下划线的):
TRAV20*02-CAVQANRGSTLGRLYF-TRAJ18*01 SEQ ID NO:34
MEKMLEC AFIVLWLQLG WLSGEDQVTQ SPEALRLQEG ESSSLNCSYT VSGLRGLFWYRQDPGKGPEF LFTKEKERLKATL TKKESFLHIT APKPEDSATY LCAVQANRGS TLGRLYFGRGTQLTVWPD
TRBV28*01-CASSLWGRLAKNIQYF-TRBD1*01-TRBJ2-4*01 SEQ ID NO:35
MGIRLL CRVAFCFLAV GLVDVKVTQS SRYLVKRTGE KVFLECVQDM DHENMFWYRQDPGLGLRLIY FKEK GDIPEGYSVS REKKERFSLI LESASTNQTS MYLCASSLWG RLAKNIQYFG AGTRLSVL
实施例4:识别HPV 16-E6表位TIHDIILECV的T细胞受体T4
全长可变链序列(CDR3序列是加下划线的):
TRAV21*02-CAVRETSGSRLTF-TRAJ58*01 SEQ ID NO:36
METLLGLL ILWLQLQWVS SKQEVTQIPA ALSVPEGENL VLNCSFTDSA IYNLQWFRQDPGKGLTSLLLQTS GRLNASLDKS SGRSTLYIAA SQPGDSATYL CAVRETSGSR LTFGEGTQLTVNPD
TRBV28*01-CASSFWGRSTDTQYF-TRBD1*01-TRBJ2-3*01 SEQ ID NO:37
MGIRLL CRVAFCFLAV GLVDVKVTQS SRYLVKRTGE KVFLECVQDM DHENMFWYRQDPGLGLRLIY FKEK GDIPEGYSVS REKKERFSLI LESASTNQTS MYLCASSFWG RSTDTQYFGP GTRLTVL
实施例5:识别HPV16-E6表位TIHDIILECV的T-细胞受体T5
全长可变链序列(CDR3序列是加下划线的):
TRAV17*01-CATVSTDSWGKKLQF-TRAJ24*02 SEQ ID NO:38
M ETLLGVSLVI LWLQLARVNS QQGEEDPQAL SIQEGENATM NCSYKTSINN LQWYRQNSGRGLVHLILKHSGRL RVTLDTSKKS SSLLITASRA ADTASYFCAT VSTDSWGKLQ FGAGTQVVVT PD
TRBV10‐3*02-CAISDSNGINIQYF-TRBD2*02-TRBJ2-4*01 SEQ ID NO:39
MRSWPG PEMGTRLFFY VALCLLWTGH MDAGITQSPR HKVTETGTPV TLRCHQTENHRYMYWYRQDP GHGLRLIHYTDKGE VSDGYSVSRS KTEDFLLTLE SATSSQTSVYFCAISDSNGI NIQYFGAGTR LSVL
TRBV28*01-CASSLWGRAGKDTQYF-TRBD2*02-TRBJ2-3*01 SEQ ID NO:40
MGIRLL CRVAFCFLAV GLVDVKVTQS SRYLVKRTGE KVFLECVQDM DHENMFWYRQDPGLGLRLIY FKEK GDIPEGYSVS REKKERFSLI LESASTNQTS MYLCASSLWG RAGKDTQYFG PGTRLTVL
实施例6:识别HPV 16-E6表位KLPQLCTEL的T细胞受体T6
全长可变链序列(CDR3序列是加下划线的):
TRAV8-6*01-CAVSLNSGNTPLVF-TRAJ29*01 SEQ ID NO:41
ML LLLVPAFQVI FTLGGTRAQS VTQLDSQVPV FEEAPVELRC NYSSSVSVYL FWYVQYPNQGLQLLLKESINGF EAEFNKSQTS FHLRKPSVHI SDTAEYFCAV SLNSGNTPLV FGKGTRLSVI AN
TRBV20-1*01-CSARDLAGNTGELFF-TRBD2*01-TRBJ2-2*01 SEQ ID NO:42
MLLLLLLLGPGSGLGAVVSQ HPSWVICKSG TSVKIECRSL DFQATTMFWY RQFPKQSLML MATTYEQGVEKDK FLINHASLTL STLTVTSAHP EDSSFYICSA RDLAGNTGEL FFGEGSRLTVL
实施例7:识别HPV 16-E7表位TLGIVCPI的T细胞受体T7
全长可变链序列(CDR3序列是加下划线的):
TRAV30*01-CGTGTDSWGKLQF-TRAJ24*02 SEQ ID NO:43
METLLKVL SGTLLWQLTW VRSQQPVQSP QAVILREGED AVINCSSSKA LYSVHWYRQKHGEAPVFLMIKGH EKISASFNEK KQQSSLYLTA SQLSYSGTYF CGTGTDSWGK LQFGAGTQVV VTPD
TRBV12‐4*01-CASSPGLAGGEQFF-TRBD2*02-TRBJ2-1*01 SEQ ID NO:44
MGSWTL CCVSLCILVA KHTDAGVIQS PRHEVTEMGQ EVTLRCKPIS GHDYLFWYRQTMMRGLELLI YIDD SGMPEDRFSA KMPNASFSTL KIQPSEPRDS AVYFCASSPG LAGGEQFFGP GTRLTVL
实施例8:识别HPV 16-E7表位TLGIVCPI的T细胞受体T8
全长可变链序列(CDR3序列是加下划线的):
TRAV22*01-CAVEPNSGNTPLVF-TRAJ29*01 SEQ ID NO:45
MKRILGAL LGLLSAQVCC VRGIQVEQSP PDLILQEGAN STLRCNFSDS VNNLQWFHQNPWGQLINLFYKQNGR LSATTVATER YSLLYISSSQ TTDSGVYFCA VEPNSGNTPL VFGKGTRLSVIAN
TRBV7-2*02或03-CASSLIISYNEQFF-TRBJ2-1*01 SEQ ID NO:46
MGTRLL FWVAFCLLGA YHTGAGVSQS PSNKVTEKGK DVELRCDPIS GHTALYWYRQRLGQGLEFLI YPDK SGLPSDRFSA ERTGESVSTL TIQRTQQEDS AVYLCASSLI ISYNEQFFGP GTRLTVL
实施例9:识别HPV 16-E7表位TLGIVCPI的T细胞受体T9
全长可变链序列(CDR3序列是加下划线的):
TRAV38-2/DV-8*01-CAYRSAPYSGAGSYQLTF-TRAJ28*01 SEQ ID NO:47
MACPGFL WALVISTCLE FSMAQTVTQS QPEMSVQEAE TVTLSCTYDT SESDYYLFWYKQPPSRQMIL VIRATENRFSVN FQKAAKSFSL KISDSQLGDA AMYFCAYRSA PYSGAGSYQL TFGKGTKLSV IPN
TRBV4-2*01-CASSQAPGLAGAEQYF-TRBD2*02-TRBJ2-7*01 SEQ ID NO:48
MGCRLL CCAVLCLLGA VPMETGVTQT PRHLVMGMTN KKSLKCEQHL GHNAMYWYKQSAKKPLELMF VTEN NSVPSRFSPE CPNSSHLFLH LHTLQPEDSA LYLCASSQAP GLAGAEQYFG PGTRLTVT
实施例10:由TCR T2、T3和T4转导的细胞系释放的干扰素γ
图6和7显示了用TCR T3和T4(图6)和T2(图7)转导的T细胞系。结果显示在附图和附图说明中。
序列表
<110> 亥姆霍兹社区***-德布鲁克-分子医学中心(MAX-DELBRÜCK-CENTRUM FÜR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT)
<120> 高亲合力HPV T细胞受体
<130> M33020WO
<150> EP15190230.1
<151> 2015-10-16
<160> 48
<170> PatentIn 3.5版
<210> 1
<211> 9
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 1
Tyr Ile Ile Phe Val Tyr Ile Pro Leu
1 5
<210> 2
<211> 9
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 2
Lys Leu Pro Gln Leu Cys Thr Glu Leu
1 5
<210> 3
<211> 10
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 3
Thr Ile His Asp Ile Ile Leu Glu Cys Val
1 5 10
<210> 4
<211> 9
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 4
Tyr Met Leu Asp Leu Gln Pro Glu Thr
1 5
<210> 5
<211> 10
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 5
Tyr Met Leu Asp Leu Gln Pro Glu Thr Thr
1 5 10
<210> 6
<211> 8
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 6
Thr Leu Gly Ile Val Cys Pro Ile
1 5
<210> 7
<211> 9
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 7
Lys Cys Ile Asp Phe Tyr Ser Arg Ile
1 5
<210> 8
<211> 9
<212> PRT
<213> 人***瘤病毒(Human papillomavirus)
<400> 8
Phe Gln Gln Leu Phe Leu Asn Thr Leu
1 5
<210> 9
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 9
Cys Ala Ala Ser Ser Tyr Asn Gln Gly Gly Lys Leu Ile Phe
1 5 10
<210> 10
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<400> 10
Cys Ile Leu Arg Asp Val Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu
1 5 10 15
Thr Phe
<210> 11
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 11
Cys Ala Ser Ser Leu Leu Ser Ser Tyr Asn Glu Gln Phe Phe
1 5 10
<210> 12
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<400> 12
Cys Ala Val Asn Val Asp Phe Asn Lys Phe Tyr Phe
1 5 10
<210> 13
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 13
Cys Ala Ser Ser Gln Asp Trp Asn Asn Glu Gln Phe Phe
1 5 10
<210> 14
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 14
Cys Ala Val Gln Ala Asn Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe
1 5 10 15
<210> 15
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 15
Cys Ala Ser Ser Leu Trp Gly Arg Leu Ala Lys Asn Ile Gln Tyr Phe
1 5 10 15
<210> 16
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 16
Cys Ala Val Arg Glu Thr Ser Gly Ser Arg Leu Thr Phe
1 5 10
<210> 17
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 17
Cys Ala Ser Ser Phe Trp Gly Arg Ser Thr Asp Thr Gln Tyr Phe
1 5 10 15
<210> 18
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 18
Cys Ala Thr Val Ser Thr Asp Ser Trp Gly Lys Lys Leu Gln Phe
1 5 10 15
<210> 19
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 19
Cys Ala Ile Ser Asp Ser Asn Gly Ile Asn Ile Gln Tyr Phe
1 5 10
<210> 20
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 20
Cys Ala Ser Ser Leu Trp Gly Arg Ala Gly Lys Asp Thr Gln Tyr Phe
1 5 10 15
<210> 21
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 21
Cys Ala Val Ser Leu Asn Ser Gly Asn Thr Pro Leu Val Phe
1 5 10
<210> 22
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 22
Cys Ser Ala Arg Asp Leu Ala Gly Asn Thr Gly Glu Leu Phe Phe
1 5 10 15
<210> 23
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<400> 23
Cys Gly Thr Gly Thr Asp Ser Trp Gly Lys Leu Gln Phe
1 5 10
<210> 24
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 24
Cys Ala Ser Ser Pro Gly Leu Ala Gly Gly Glu Gln Phe Phe
1 5 10
<210> 25
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 25
Cys Ala Val Glu Pro Asn Ser Gly Asn Thr Pro Leu Val Phe
1 5 10
<210> 26
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<400> 26
Cys Ala Ser Ser Leu Ile Ile Ser Tyr Asn Glu Gln Phe Phe
1 5 10
<210> 27
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<400> 27
Cys Ala Tyr Arg Ser Ala Pro Tyr Ser Gly Ala Gly Ser Tyr Gln Leu
1 5 10 15
Thr Phe
<210> 28
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<400> 28
Cys Ala Ser Ser Gln Ala Pro Gly Leu Ala Gly Ala Glu Gln Tyr Phe
1 5 10 15
<210> 29
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 29
Met Thr Ser Ile Arg Ala Val Phe Ile Phe Leu Trp Leu Gln Leu Asp
1 5 10 15
Leu Val Asn Gly Glu Asn Val Glu Gln His Pro Ser Thr Leu Ser Val
20 25 30
Gln Glu Gly Asp Ser Ala Val Ile Lys Cys Thr Tyr Ser Asp Ser Ala
35 40 45
Ser Asn Tyr Phe Pro Trp Tyr Lys Gln Glu Leu Gly Lys Gly Pro Gln
50 55 60
Leu Ile Ile Asp Ile Arg Ser Asn Val Gly Glu Lys Lys Asp Gln Arg
65 70 75 80
Ile Ala Val Thr Leu Asn Lys Thr Ala Lys His Phe Ser Leu His Ile
85 90 95
Thr Glu Thr Gln Pro Glu Asp Ser Ala Val Tyr Phe Cys Ala Ala Ser
100 105 110
Ser Tyr Asn Gln Gly Gly Lys Leu Ile Phe Gly Gln Gly Thr Glu Leu
115 120 125
Ser Val Lys Pro Asn
130
<210> 30
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 30
Met Lys Leu Val Thr Ser Ile Thr Val Leu Leu Ser Leu Gly Ile Met
1 5 10 15
Gly Asp Ala Lys Thr Thr Gln Pro Asn Ser Met Glu Ser Asn Glu Glu
20 25 30
Glu Pro Val His Leu Pro Cys Asn His Ser Thr Ile Ser Gly Thr Asp
35 40 45
Tyr Ile His Trp Tyr Arg Gln Leu Pro Ser Gln Gly Pro Glu Tyr Val
50 55 60
Ile His Gly Leu Thr Ser Asn Val Asn Asn Arg Met Ala Ser Leu Ala
65 70 75 80
Ile Ala Glu Asp Arg Lys Ser Ser Thr Leu Ile Leu His Arg Ala Thr
85 90 95
Leu Arg Asp Ala Ala Val Tyr Tyr Cys Ile Leu Arg Asp Val Asn Ala
100 105 110
Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe Gly Gln Gly Thr Ile Leu
115 120 125
Thr Val His Pro Asn
130
<210> 31
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 31
Met Asp Ser Trp Thr Phe Cys Cys Val Ser Leu Cys Ile Leu Val Ala
1 5 10 15
Lys His Thr Asp Ala Gly Val Ile Gln Ser Pro Arg His Glu Val Thr
20 25 30
Glu Met Gly Gln Glu Val Thr Leu Arg Cys Lys Pro Ile Ser Gly His
35 40 45
Asn Ser Leu Phe Trp Tyr Arg Gln Thr Met Met Arg Gly Leu Glu Leu
50 55 60
Leu Ile Tyr Phe Asn Asn Asn Val Pro Ile Asp Asp Ser Gly Met Pro
65 70 75 80
Glu Asp Arg Phe Ser Ala Lys Met Pro Asn Ala Ser Phe Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ser Glu Pro Arg Asp Ser Ala Val Tyr Phe Cys Ala
100 105 110
Ser Ser Leu Leu Ser Ser Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu
130
<210> 32
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 32
Met Met Lys Ser Leu Arg Val Leu Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ser Trp Val Trp Ser Gln Gln Lys Glu Val Glu Gln Asn Ser Gly Pro
20 25 30
Leu Ser Val Pro Glu Gly Ala Ile Ala Ser Leu Asn Cys Thr Tyr Ser
35 40 45
Asp Arg Gly Ser Gln Ser Phe Phe Trp Tyr Arg Gln Tyr Ser Gly Lys
50 55 60
Ser Pro Glu Leu Ile Met Ser Ile Tyr Ser Asn Gly Asp Lys Glu Asp
65 70 75 80
Gly Arg Phe Thr Ala Gln Leu Asn Lys Ala Ser Gln Tyr Val Ser Leu
85 90 95
Leu Ile Arg Asp Ser Gln Pro Ser Asp Ser Ala Thr Tyr Leu Cys Ala
100 105 110
Val Asn Val Asp Phe Asn Lys Phe Tyr Phe Gly Ser Gly Thr Lys Leu
115 120 125
Asn Val Lys Pro Asn
130
<210> 33
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 33
Met Gly Cys Arg Leu Leu Cys Cys Ala Val Leu Cys Leu Leu Gly Ala
1 5 10 15
Val Pro Ile Asp Thr Glu Val Thr Gln Thr Pro Lys His Leu Val Met
20 25 30
Gly Met Thr Asn Lys Lys Ser Leu Lys Cys Glu Gln His Met Gly His
35 40 45
Arg Ala Met Tyr Trp Tyr Lys Gln Lys Ala Lys Lys Pro Pro Glu Leu
50 55 60
Met Phe Val Tyr Ser Tyr Glu Lys Leu Ser Ile Asn Glu Ser Val Pro
65 70 75 80
Ser Arg Phe Ser Pro Glu Cys Pro Asn Ser Ser Leu Leu Asn Leu His
85 90 95
Leu His Ala Leu Gln Pro Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
100 105 110
Ser Gln Asp Trp Asn Asn Glu Gln Phe Phe Gly Pro Gly Thr Arg Leu
115 120 125
Thr Val Leu
130
<210> 34
<211> 135
<212> PRT
<213> 智人(Homo sapiens)
<400> 34
Met Glu Lys Met Leu Glu Cys Ala Phe Ile Val Leu Trp Leu Gln Leu
1 5 10 15
Gly Trp Leu Ser Gly Glu Asp Gln Val Thr Gln Ser Pro Glu Ala Leu
20 25 30
Arg Leu Gln Glu Gly Glu Ser Ser Ser Leu Asn Cys Ser Tyr Thr Val
35 40 45
Ser Gly Leu Arg Gly Leu Phe Trp Tyr Arg Gln Asp Pro Gly Lys Gly
50 55 60
Pro Glu Phe Leu Phe Thr Leu Tyr Ser Ala Gly Glu Glu Lys Glu Lys
65 70 75 80
Glu Arg Leu Lys Ala Thr Leu Thr Lys Lys Glu Ser Phe Leu His Ile
85 90 95
Thr Ala Pro Lys Pro Glu Asp Ser Ala Thr Tyr Leu Cys Ala Val Gln
100 105 110
Ala Asn Arg Gly Ser Thr Leu Gly Arg Leu Tyr Phe Gly Arg Gly Thr
115 120 125
Gln Leu Thr Val Trp Pro Asp
130 135
<210> 35
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 35
Met Gly Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Leu Trp Gly Arg Leu Ala Lys Asn Ile Gln Tyr Phe Gly Ala Gly
115 120 125
Thr Arg Leu Ser Val Leu
130
<210> 36
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 36
Met Glu Thr Leu Leu Gly Leu Leu Ile Leu Trp Leu Gln Leu Gln Trp
1 5 10 15
Val Ser Ser Lys Gln Glu Val Thr Gln Ile Pro Ala Ala Leu Ser Val
20 25 30
Pro Glu Gly Glu Asn Leu Val Leu Asn Cys Ser Phe Thr Asp Ser Ala
35 40 45
Ile Tyr Asn Leu Gln Trp Phe Arg Gln Asp Pro Gly Lys Gly Leu Thr
50 55 60
Ser Leu Leu Leu Ile Gln Ser Ser Gln Arg Glu Gln Thr Ser Gly Arg
65 70 75 80
Leu Asn Ala Ser Leu Asp Lys Ser Ser Gly Arg Ser Thr Leu Tyr Ile
85 90 95
Ala Ala Ser Gln Pro Gly Asp Ser Ala Thr Tyr Leu Cys Ala Val Arg
100 105 110
Glu Thr Ser Gly Ser Arg Leu Thr Phe Gly Glu Gly Thr Gln Leu Thr
115 120 125
Val Asn Pro Asp
130
<210> 37
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 37
Met Gly Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Phe Trp Gly Arg Ser Thr Asp Thr Gln Tyr Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu
130
<210> 38
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 38
Met Glu Thr Leu Leu Gly Val Ser Leu Val Ile Leu Trp Leu Gln Leu
1 5 10 15
Ala Arg Val Asn Ser Gln Gln Gly Glu Glu Asp Pro Gln Ala Leu Ser
20 25 30
Ile Gln Glu Gly Glu Asn Ala Thr Met Asn Cys Ser Tyr Lys Thr Ser
35 40 45
Ile Asn Asn Leu Gln Trp Tyr Arg Gln Asn Ser Gly Arg Gly Leu Val
50 55 60
His Leu Ile Leu Ile Arg Ser Asn Glu Arg Glu Lys His Ser Gly Arg
65 70 75 80
Leu Arg Val Thr Leu Asp Thr Ser Lys Lys Ser Ser Ser Leu Leu Ile
85 90 95
Thr Ala Ser Arg Ala Ala Asp Thr Ala Ser Tyr Phe Cys Ala Thr Val
100 105 110
Ser Thr Asp Ser Trp Gly Lys Leu Gln Phe Gly Ala Gly Thr Gln Val
115 120 125
Val Val Thr Pro Asp
130
<210> 39
<211> 140
<212> PRT
<213> 智人(Homo sapiens)
<400> 39
Met Arg Ser Trp Pro Gly Pro Glu Met Gly Thr Arg Leu Phe Phe Tyr
1 5 10 15
Val Ala Leu Cys Leu Leu Trp Thr Gly His Met Asp Ala Gly Ile Thr
20 25 30
Gln Ser Pro Arg His Lys Val Thr Glu Thr Gly Thr Pro Val Thr Leu
35 40 45
Arg Cys His Gln Thr Glu Asn His Arg Tyr Met Tyr Trp Tyr Arg Gln
50 55 60
Asp Pro Gly His Gly Leu Arg Leu Ile His Tyr Ser Tyr Gly Val Lys
65 70 75 80
Asp Thr Asp Lys Gly Glu Val Ser Asp Gly Tyr Ser Val Ser Arg Ser
85 90 95
Lys Thr Glu Asp Phe Leu Leu Thr Leu Glu Ser Ala Thr Ser Ser Gln
100 105 110
Thr Ser Val Tyr Phe Cys Ala Ile Ser Asp Ser Asn Gly Ile Asn Ile
115 120 125
Gln Tyr Phe Gly Ala Gly Thr Arg Leu Ser Val Leu
130 135 140
<210> 40
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 40
Met Gly Ile Arg Leu Leu Cys Arg Val Ala Phe Cys Phe Leu Ala Val
1 5 10 15
Gly Leu Val Asp Val Lys Val Thr Gln Ser Ser Arg Tyr Leu Val Lys
20 25 30
Arg Thr Gly Glu Lys Val Phe Leu Glu Cys Val Gln Asp Met Asp His
35 40 45
Glu Asn Met Phe Trp Tyr Arg Gln Asp Pro Gly Leu Gly Leu Arg Leu
50 55 60
Ile Tyr Phe Ser Tyr Asp Val Lys Met Lys Glu Lys Gly Asp Ile Pro
65 70 75 80
Glu Gly Tyr Ser Val Ser Arg Glu Lys Lys Glu Arg Phe Ser Leu Ile
85 90 95
Leu Glu Ser Ala Ser Thr Asn Gln Thr Ser Met Tyr Leu Cys Ala Ser
100 105 110
Ser Leu Trp Gly Arg Ala Gly Lys Asp Thr Gln Tyr Phe Gly Pro Gly
115 120 125
Thr Arg Leu Thr Val Leu
130
<210> 41
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
<400> 41
Met Leu Leu Leu Leu Val Pro Ala Phe Gln Val Ile Phe Thr Leu Gly
1 5 10 15
Gly Thr Arg Ala Gln Ser Val Thr Gln Leu Asp Ser Gln Val Pro Val
20 25 30
Phe Glu Glu Ala Pro Val Glu Leu Arg Cys Asn Tyr Ser Ser Ser Val
35 40 45
Ser Val Tyr Leu Phe Trp Tyr Val Gln Tyr Pro Asn Gln Gly Leu Gln
50 55 60
Leu Leu Leu Lys Tyr Leu Ser Gly Ser Thr Leu Val Glu Ser Ile Asn
65 70 75 80
Gly Phe Glu Ala Glu Phe Asn Lys Ser Gln Thr Ser Phe His Leu Arg
85 90 95
Lys Pro Ser Val His Ile Ser Asp Thr Ala Glu Tyr Phe Cys Ala Val
100 105 110
Ser Leu Asn Ser Gly Asn Thr Pro Leu Val Phe Gly Lys Gly Thr Arg
115 120 125
Leu Ser Val Ile Ala Asn
130
<210> 42
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 42
Met Leu Leu Leu Leu Leu Leu Leu Gly Pro Gly Ser Gly Leu Gly Ala
1 5 10 15
Val Val Ser Gln His Pro Ser Trp Val Ile Cys Lys Ser Gly Thr Ser
20 25 30
Val Lys Ile Glu Cys Arg Ser Leu Asp Phe Gln Ala Thr Thr Met Phe
35 40 45
Trp Tyr Arg Gln Phe Pro Lys Gln Ser Leu Met Leu Met Ala Thr Ser
50 55 60
Asn Glu Gly Ser Lys Ala Thr Tyr Glu Gln Gly Val Glu Lys Asp Lys
65 70 75 80
Phe Leu Ile Asn His Ala Ser Leu Thr Leu Ser Thr Leu Thr Val Thr
85 90 95
Ser Ala His Pro Glu Asp Ser Ser Phe Tyr Ile Cys Ser Ala Arg Asp
100 105 110
Leu Ala Gly Asn Thr Gly Glu Leu Phe Phe Gly Glu Gly Ser Arg Leu
115 120 125
Thr Val Leu
130
<210> 43
<211> 132
<212> PRT
<213> 智人(Homo sapiens)
<400> 43
Met Glu Thr Leu Leu Lys Val Leu Ser Gly Thr Leu Leu Trp Gln Leu
1 5 10 15
Thr Trp Val Arg Ser Gln Gln Pro Val Gln Ser Pro Gln Ala Val Ile
20 25 30
Leu Arg Glu Gly Glu Asp Ala Val Ile Asn Cys Ser Ser Ser Lys Ala
35 40 45
Leu Tyr Ser Val His Trp Tyr Arg Gln Lys His Gly Glu Ala Pro Val
50 55 60
Phe Leu Met Ile Leu Leu Lys Gly Gly Glu Gln Lys Gly His Glu Lys
65 70 75 80
Ile Ser Ala Ser Phe Asn Glu Lys Lys Gln Gln Ser Ser Leu Tyr Leu
85 90 95
Thr Ala Ser Gln Leu Ser Tyr Ser Gly Thr Tyr Phe Cys Gly Thr Gly
100 105 110
Thr Asp Ser Trp Gly Lys Leu Gln Phe Gly Ala Gly Thr Gln Val Val
115 120 125
Val Thr Pro Asp
130
<210> 44
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 44
Met Gly Ser Trp Thr Leu Cys Cys Val Ser Leu Cys Ile Leu Val Ala
1 5 10 15
Lys His Thr Asp Ala Gly Val Ile Gln Ser Pro Arg His Glu Val Thr
20 25 30
Glu Met Gly Gln Glu Val Thr Leu Arg Cys Lys Pro Ile Ser Gly His
35 40 45
Asp Tyr Leu Phe Trp Tyr Arg Gln Thr Met Met Arg Gly Leu Glu Leu
50 55 60
Leu Ile Tyr Phe Asn Asn Asn Val Pro Ile Asp Asp Ser Gly Met Pro
65 70 75 80
Glu Asp Arg Phe Ser Ala Lys Met Pro Asn Ala Ser Phe Ser Thr Leu
85 90 95
Lys Ile Gln Pro Ser Glu Pro Arg Asp Ser Ala Val Tyr Phe Cys Ala
100 105 110
Ser Ser Pro Gly Leu Ala Gly Gly Glu Gln Phe Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu
130
<210> 45
<211> 131
<212> PRT
<213> 智人(Homo sapiens)
<400> 45
Met Lys Arg Ile Leu Gly Ala Leu Leu Gly Leu Leu Ser Ala Gln Val
1 5 10 15
Cys Cys Val Arg Gly Ile Gln Val Glu Gln Ser Pro Pro Asp Leu Ile
20 25 30
Leu Gln Glu Gly Ala Asn Ser Thr Leu Arg Cys Asn Phe Ser Asp Ser
35 40 45
Val Asn Asn Leu Gln Trp Phe His Gln Asn Pro Trp Gly Gln Leu Ile
50 55 60
Asn Leu Phe Tyr Ile Pro Ser Gly Thr Lys Gln Asn Gly Arg Leu Ser
65 70 75 80
Ala Thr Thr Val Ala Thr Glu Arg Tyr Ser Leu Leu Tyr Ile Ser Ser
85 90 95
Ser Gln Thr Thr Asp Ser Gly Val Tyr Phe Cys Ala Val Glu Pro Asn
100 105 110
Ser Gly Asn Thr Pro Leu Val Phe Gly Lys Gly Thr Arg Leu Ser Val
115 120 125
Ile Ala Asn
130
<210> 46
<211> 133
<212> PRT
<213> 智人(Homo sapiens)
<400> 46
Met Gly Thr Arg Leu Leu Phe Trp Val Ala Phe Cys Leu Leu Gly Ala
1 5 10 15
Tyr His Thr Gly Ala Gly Val Ser Gln Ser Pro Ser Asn Lys Val Thr
20 25 30
Glu Lys Gly Lys Asp Val Glu Leu Arg Cys Asp Pro Ile Ser Gly His
35 40 45
Thr Ala Leu Tyr Trp Tyr Arg Gln Arg Leu Gly Gln Gly Leu Glu Phe
50 55 60
Leu Ile Tyr Phe Gln Gly Asn Ser Ala Pro Asp Lys Ser Gly Leu Pro
65 70 75 80
Ser Asp Arg Phe Ser Ala Glu Arg Thr Gly Glu Ser Val Ser Thr Leu
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Thr Ile Gln Arg Thr Gln Gln Glu Asp Ser Ala Val Tyr Leu Cys Ala
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Ser Ser Leu Ile Ile Ser Tyr Asn Glu Gln Phe Phe Gly Pro Gly Thr
115 120 125
Arg Leu Thr Val Leu
130
<210> 47
<211> 140
<212> PRT
<213> 智人(Homo sapiens)
<400> 47
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu
1 5 10 15
Glu Phe Ser Met Ala Gln Thr Val Thr Gln Ser Gln Pro Glu Met Ser
20 25 30
Val Gln Glu Ala Glu Thr Val Thr Leu Ser Cys Thr Tyr Asp Thr Ser
35 40 45
Glu Ser Asp Tyr Tyr Leu Phe Trp Tyr Lys Gln Pro Pro Ser Arg Gln
50 55 60
Met Ile Leu Val Ile Arg Gln Glu Ala Tyr Lys Gln Gln Asn Ala Thr
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Glu Asn Arg Phe Ser Val Asn Phe Gln Lys Ala Ala Lys Ser Phe Ser
85 90 95
Leu Lys Ile Ser Asp Ser Gln Leu Gly Asp Ala Ala Met Tyr Phe Cys
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Ala Tyr Arg Ser Ala Pro Tyr Ser Gly Ala Gly Ser Tyr Gln Leu Thr
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<210> 48
<211> 134
<212> PRT
<213> 智人(Homo sapiens)
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Asn Ala Met Tyr Trp Tyr Lys Gln Ser Ala Lys Lys Pro Leu Glu Leu
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Ser Arg Phe Ser Pro Glu Cys Pro Asn Ser Ser His Leu Phe Leu His
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Leu His Thr Leu Gln Pro Glu Asp Ser Ala Leu Tyr Leu Cys Ala Ser
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Ser Gln Ala Pro Gly Leu Ala Gly Ala Glu Gln Tyr Phe Gly Pro Gly
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Thr Arg Leu Thr Val Thr
130
Claims (18)
1.HPV特异性抗原识别构建体,其为T细胞受体或其片段,所述抗原识别构建体在其α链中包含序列为VSGLRG的CDR1,序列为LYSAGEE的CDR2和序列为CAVQANRGSTLGRLYF的CDR3;和在其β链中包含序列为MDHEN的CDR1,序列为SYDVKM的CDR2和序列为CASSLWGRLAKNIQYF的CDR3。
2.如权利要求1所述的抗原识别构建体,其是由T细胞受体α链和T细胞受体β链组成的T细胞受体或其片段。
3.如权利要求1或2所述的抗原识别构建体,其中所述T细胞受体包含如SEQ ID NO:34和35所示的可变序列。
4.核酸,其编码权利要求1至3中任一项所述的抗原识别构建体。
5.载体,其包含权利要求4所述的核酸。
6.分离的宿主细胞,其包含权利要求1至3中任一项所述的抗原识别构建体,或权利要求4所述的核酸,或权利要求5所述的载体,其中所述分离的宿主细胞是淋巴细胞。
7.如权利要求6所述的分离的宿主细胞,其是T淋巴细胞。
8.如权利要求6所述的分离的宿主细胞,其是CD4或CD8阳性T细胞。
9.权利要求1至3中任一项所述的抗原识别构建体,或权利要求4所述的核酸,或权利要求5所述的载体,或权利要求6-至8中任一项所述的分离的宿主细胞在制备药物中的用途。
10.如权利要求9所述的用途,其中所述药物被用于诊断、预防和/或治疗感染性疾病或增殖性疾病中。
11.如权利要求9所述的用途,其中所述药物被用于诊断、预防和/或治疗恶性或良性肿瘤疾病中。
12.如权利要求9至11中任一项所述的用途,其中所述药物被用于免疫疗法中。
13.如权利要求9至11中任一项所述的用途,其中所述药物被用于过继性T细胞疗法中。
14.用于制备表达HPV特异性抗原识别构建体的细胞系的体外方法,其包括:
a.提供适合的宿主细胞,
b.提供编码权利要求1至3中任一项的抗原识别构建体的基因构建体,
c.将所述基因构建体引入所述适合的宿主细胞中,
d.由所述适合的宿主细胞表达所述基因构建体。
15.如权利要求14所述的方法,其中所述细胞是哺乳动物的T细胞。
16.如权利要求14所述的方法,其中所述细胞是人的T细胞。
17.如权利要求14至16中任一项所述的方法,其还包括从所述细胞纯化所述抗原识别构建体。
18.如权利要求14至16中任一项所述的方法,其还包括在T细胞中重组翻译的抗原识别构建体片段。
Applications Claiming Priority (3)
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EP15190230.1 | 2015-10-16 | ||
EP15190230.1A EP3156067A1 (en) | 2015-10-16 | 2015-10-16 | High avidity hpv t-cell receptors |
PCT/EP2016/074612 WO2017064198A1 (en) | 2015-10-16 | 2016-10-13 | High avidity hpv t-cell receptors |
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CN108135998B true CN108135998B (zh) | 2023-05-09 |
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EP (2) | EP3156067A1 (zh) |
JP (1) | JP7000315B2 (zh) |
CN (1) | CN108135998B (zh) |
AU (1) | AU2016336817C1 (zh) |
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WO (1) | WO2017064198A1 (zh) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102017114737A1 (de) * | 2017-06-30 | 2019-01-03 | Immatics Biotechnologies Gmbh | Neue T-Zellrezeptoren und deren Verwendung in Immuntherapie |
KR20200104284A (ko) * | 2017-10-03 | 2020-09-03 | 주노 쎄러퓨티크스 인코퍼레이티드 | Hpv-특이적 결합 분자 |
CN109053879B (zh) * | 2018-08-22 | 2020-12-25 | 深圳市宝安区中心医院 | 一种治疗***的scFv抗体及其应用 |
CN113072635B (zh) * | 2020-01-06 | 2023-08-25 | 香雪生命科学技术(广东)有限公司 | 一种识别hpv抗原的t细胞受体及其编码序列 |
WO2021155518A1 (en) * | 2020-02-05 | 2021-08-12 | Tcrcure Biopharma Corp | Anti-hpv t cell receptors and engineered cells |
CN113321726B (zh) * | 2020-02-28 | 2024-05-28 | 香雪生命科学技术(广东)有限公司 | 一种识别hpv的t细胞受体 |
WO2021191677A1 (en) * | 2020-03-23 | 2021-09-30 | The Council Of The Queensland Institute Of Medical Research | Compositions and methods for targeting hpv-infected cells |
CN116096740A (zh) * | 2020-06-09 | 2023-05-09 | 得克萨斯州大学***董事会 | 经改造t细胞受体和使用方法 |
WO2022060904A1 (en) | 2020-09-16 | 2022-03-24 | Obsidian Therapeutics, Inc. | Compositions and methods for expression of t-cell receptors with small molecule-regulated cd40l in t cells |
CN114539385A (zh) * | 2020-11-26 | 2022-05-27 | 香雪生命科学技术(广东)有限公司 | 一种识别hpv抗原的tcr |
CN114853878A (zh) * | 2021-02-03 | 2022-08-05 | 香雪生命科学技术(广东)有限公司 | 一种针对hpv的高亲和力tcr |
CN117693508A (zh) | 2021-03-03 | 2024-03-12 | 朱诺治疗学股份有限公司 | T细胞疗法和dgk抑制剂的组合 |
WO2023014337A1 (en) * | 2021-08-04 | 2023-02-09 | GUERRERO PRESTON Rafael | Viral and host biomarkers for early detection, therapeutic effectiveness, and relapse monitoring of cancer linked to severe acute respiratory syndrome coronavirus 2 and human papilloma virus |
WO2024054944A1 (en) | 2022-09-08 | 2024-03-14 | Juno Therapeutics, Inc. | Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012038055A1 (en) * | 2010-09-20 | 2012-03-29 | Unicell Gmbh | Antigen-specific t cell receptors and t cell epitopes |
WO2015009606A1 (en) * | 2013-07-15 | 2015-01-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-human papillomavirus 16 e6 t cell receptors |
WO2015092362A1 (en) * | 2013-12-18 | 2015-06-25 | Immunocore Limited | T cell receptor binding to alwgpdpaaa, derived from human pre-pro insulin (ppi) protein |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69127627T2 (de) | 1990-08-29 | 1998-02-19 | Genpharm Int | Produktion und Nützung nicht-menschliche transgentiere zur Produktion heterologe Antikörper |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5714352A (en) | 1996-03-20 | 1998-02-03 | Xenotech Incorporated | Directed switch-mediated DNA recombination |
JP2004511425A (ja) | 2000-02-08 | 2004-04-15 | ザ ペン ステート リサーチ ファウンデーション | 免疫療法に使用されるインターロイキン13受容体サブユニットアルファー2 |
US20070218080A1 (en) | 2006-03-14 | 2007-09-20 | Mackay Memorial Hospital | Peptide antigen of human papillomavirus type 16 and application thereof |
AU2008304555A1 (en) * | 2007-09-25 | 2009-04-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Modified T cell receptors and related materials and methods |
TWI507413B (zh) | 2010-11-15 | 2015-11-11 | Nat Health Research Institutes | 脂質化多抗原表位疫苗 |
WO2013105856A1 (en) | 2012-01-13 | 2013-07-18 | Apo-T B.V. | Aberrant cell-restricted immunoglobulins provided with a toxic moiety |
AU2013281327A1 (en) | 2012-06-26 | 2015-01-22 | Apo-T B.V. | Binding molecules targeting pathogens |
US10202640B2 (en) * | 2014-05-07 | 2019-02-12 | The Board Of Trustees Of The Leland Stanford Junior University | Single cell analysis of T cells using high-throughput multiplex amplification and deep sequencing |
-
2015
- 2015-10-16 EP EP15190230.1A patent/EP3156067A1/en not_active Withdrawn
-
2016
- 2016-10-13 WO PCT/EP2016/074612 patent/WO2017064198A1/en active Application Filing
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- 2016-10-13 CN CN201680060361.2A patent/CN108135998B/zh active Active
- 2016-10-13 JP JP2018519710A patent/JP7000315B2/ja active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012038055A1 (en) * | 2010-09-20 | 2012-03-29 | Unicell Gmbh | Antigen-specific t cell receptors and t cell epitopes |
CN103249430A (zh) * | 2010-09-20 | 2013-08-14 | 生物技术公司 | 抗原特异性t细胞受体和t细胞表位 |
WO2015009606A1 (en) * | 2013-07-15 | 2015-01-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-human papillomavirus 16 e6 t cell receptors |
WO2015092362A1 (en) * | 2013-12-18 | 2015-06-25 | Immunocore Limited | T cell receptor binding to alwgpdpaaa, derived from human pre-pro insulin (ppi) protein |
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AU2016336817C1 (en) | 2021-05-13 |
AU2016336817B9 (en) | 2021-02-11 |
JP2018535668A (ja) | 2018-12-06 |
US11401316B2 (en) | 2022-08-02 |
WO2017064198A1 (en) | 2017-04-20 |
US20190062398A1 (en) | 2019-02-28 |
CA3001395A1 (en) | 2017-04-20 |
JP7000315B2 (ja) | 2022-02-04 |
AU2016336817B2 (en) | 2021-02-04 |
EP3156067A1 (en) | 2017-04-19 |
CN108135998A (zh) | 2018-06-08 |
EP3362090A1 (en) | 2018-08-22 |
AU2016336817A1 (en) | 2018-05-31 |
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