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用含有公共识别基序的高特异性异基因T细胞靶向治疗B细胞宫颈炎

异体T细胞可能用于治疗宫颈炎具有重要的临床意义。由于大多数肿瘤抗原都代表了自身的蛋白,因此高亲和力的肿瘤特异性T细胞可从患者体内被广泛地清除;相反,主要组织相容性复合体(MHC)错配的供体的T细胞并没有被系统地清除。目前,有关肽简并性或多特异性的证据证实了可以将HLA或肽复合物作为治疗靶标。在本研究中,我们将HLA-A*0201阴性的T细胞与自体树突状细胞共培养,生成HLA-A*0201与B细胞抗原CD20p的复合物。所有供体均得到了CD8+活化的HLA-A*0201/CD20p五聚体T细胞。这种多克隆细胞具有精密的肽以及MHC特异性,同时能够有效地杀伤HLA-A*0201阳性的B细胞,包括初级慢性淋巴细胞宫颈炎细胞。T细胞受体序列表现出一种新的保守性,并且在TCRβ链的互补性决定区3和J区(而非V区)存在广泛的同源性。令人惊讶的是,供体的HLA是不同的并且他们的TCR组分基本没有重叠。本次研究证明了首个异基因HLA/肽复合物的公共识别基序。同种T细胞或T细胞受体可以提供抗宫颈炎移植物而不引起移植物抗宿主病。(中国生物治疗网 学术部译)

原文推荐

Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif

IW Abrahamsen1,2,3,E Stronen1,2,3,SWa¨lchli2,JN Johansen2,S Kjellevoll2, S Kumari2, M Komada2, G Gaudernack2, G Tjonnfjord3,4, M Toebes5, TN Schumacher5, F Lund-Johansen1 and J Olweus2,3

The possibility that allogeneic T cells may be targeted to leukemia has important therapeutic implications. As most tumor antigens represent self-proteins, high-avidity tumor-specific T cells are largely deleted from the repertoire of the patient. In contrast, T cells from major histocompatibility complex (MHC)-mismatched donors provide naive repertoires wherein such cells have not been systematically eliminated. Yet, evidence for peptide degeneracy or poly-specificity warrants caution in the use of foreign human leukocyte antigen (HLA) or peptide complexes as therapeutic targets. Here, we cocultured HLA-A*0201-negative T cells with autologous dendritic cells engineered to present HLA-A*0201 complexed with a peptide from the B cell antigen CD20 (CD20p). HLA-A*0201/CD20p pentamer-reactive CD8+ T cells were readily obtained from all donors. The polyclonal cells showed exquisite peptide and MHC specificity, and efficiently killed HLA-A*0201-positive B cells, including primary chronic lymphocytic leukemia cells. The T cell receptor (TCR) sequences displayed a novel type of conservation, with extensive homology in the TCR βchain complementarity-determining region 3 and in J, but not V, region. This is surprising, as the donors were HLA disparate and their TCR repertoires are expected to show little overlap. The results demonstrate the first public recognition motif for an allogeneic HLA/peptide complex. The allo-restricted T cells or TCRs could provide graft-versus-leukemia in the absence of graft-versus-host disease.

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Tag: 宫颈炎 T细胞治疗 宫颈炎治疗
keywords:T细胞治疗,宫颈炎,宫颈炎治疗
刘爱国 院长
梅蔚德 教授
姜永健 教授
洪孝英 教授
许伯寿 教授