T cell receptor-engineered T cells derived from target human leukocyte antigen-DPB1-specific T cell can be a potential tool for therapy against leukemia relapse following allogeneic hematopoietic cell transplantation.
T cell receptor-engineered T cells derived from target human leukocyte antigen-DPB1-specific T cell can be a potential tool for therapy against leukemia relapse following allogeneic hematopoietic cell transplantation.
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DOI：
10.18999/nagjms.85.4.779
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发表时间：
2023-11
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
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作者：
人类白细胞抗原(HLA)-DPB1抗原在来自HLA 10/10匹配的非亲属供体的异基因造血干细胞移植（allogenic hematopoticticstem cell transplantation, hsct）中约70%存在不匹配。hla - dp错配移植被证明与急性移植物抗宿主病（GVHD）的增加和由于移植物抗白血病（GVL）效应而降低的白血病复发风险相关。如果在非炎症条件下进行免疫治疗，靶向不匹配的HLA-DP被认为是治疗同种异体hct后白血病的合理方法。因此，我们从健康志愿者供体中分离出识别错配HLA-DPB1的CD4+ T细胞克隆，并生成T细胞受体（TCR）基因修饰的T细胞，用于未来的临床应用。对候选克隆#17表达TCR的TCR- t细胞的详细分析表明，它对髓系和单核细胞白血病细胞系具有特异性，甚至表达低水平的靶向HLA-DP。然而，它们对具有大量靶向HLA-DP表达的非造血细胞系没有反应，这表明TCR识别的抗原肽仅存在于某些造血细胞中。本研究表明，通过仔细的特异性分析，通过基因转移诱导HLA-DP特异性T细胞是可行的，包括造血细胞谱系来源的肽和克隆的TCR cDNA重定向T细胞。
Human leukocyte antigen (HLA)-DPB1 antigens are mismatched in approximately 70% of allogeneic hematopoietic stem cell transplantations (allo-HSCT) from HLA 10/10 matched unrelated donors. HLA-DP-mismatched transplantation was shown to be associated with an increase in acute graft-versus-host disease (GVHD) and a decreased risk of leukemia relapse due to the graft-versus-leukemia (GVL) effect. Immunotherapy targeting mismatched HLA-DP is considered reasonable to treat leukemia following allo-HCT if performed under non-inflammatory conditions. Therefore, we isolated CD4+ T cell clones that recognize mismatched HLA-DPB1 from healthy volunteer donors and generated T cell receptor (TCR)-gene-modified T cells for future clinical applications. Detailed analysis of TCR-T cells expressing TCR from candidate clone #17 demonstrated specificity to myeloid and monocytic leukemia cell lines that even expressed low levels of targeted HLA-DP. However, they did not react to non-hematopoietic cell lines with a substantial level of targeted HLA-DP expression, suggesting that the TCR recognized antigenic peptide is only present in some hematopoietic cells. This study demonstrated that induction of T cells specific for HLA-DP, consisting of hematopoietic cell lineage-derived peptide and redirection of T cells with cloned TCR cDNA by gene transfer, is feasible when using careful specificity analysis.
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影响因子：
10.1
作者：
Laghmouchi A;Hoogstraten C;van Balen P;Falkenburg JHF;Jedema I
通讯作者：
Jedema I
影响因子：
4.7
作者：
通讯作者：
--
影响因子：
4.3
作者：
Miller, Jeffrey S.;Warren, Edus H.;van den Brink, Marcel R. M.;Ritz, Jerome;Shlomchik, Warren D.;Murphy, William J.;Barrett, A. John;Kolb, Hans Jochem;Giralt, Sergio;Bishop, Michael R.;Blazar, Bruce R.;Falkenburg, J. H. Frederik
通讯作者：
Falkenburg, J. H. Frederik
影响因子：
7.5
作者：
Martin, Paul J.;Levine, David M.;Storer, Barry E.;Sather, Cassandra L.;Spellman, Stephen R.;Hansen, John A.
通讯作者：
Hansen, John A.