2022年6月22日 · In clinical trials, WT1 is targeted using peptide-based or dendritic cell-based vaccines and T-cell receptor (TCR)-based therapies. Antitumor reactivities were reported, but T-cell reactivity is hampered by self-tolerance to WT1 and limited number of WT1 peptides, which were thus far selected based on HLA peptide binding algorithms.

The TCR sequences of four T-cell clones were analyzed and TCR gene transfer into CD8+ T cells installed antitumor reactivity against WT1-expressing solid tumor cell lines, primary acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples.

2019年6月24日 · Nature Medicine - Donor-derived, EBV-specific CD8+ T cells engineered to express a high-affinity WT1-specific TCR established persistent T cell responses that safely prevented post-HCT...

2017年11月2日 · A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in-human trial of TCR-gene transduced T-cell (TCR-T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells.

2023年4月4日 · TCR-T技术是利用基因工程技术，将人体内T细胞中可以定向识别肿瘤细胞的T细胞受体（TCR）的基因，转导入癌症病人的T细胞内，并在体外进行扩增后回输，使癌症病人的T细胞可以精准定向识别、杀伤肿瘤，并在患者体内形成记忆T细胞，防治肿瘤复发。 相较CAR-T技术，TCR-T技术对实体瘤则效果更好。 WT1 （Wilm's Tumor 1）是一个著名的肿瘤相关抗原（TAA），在成人仅在少量的正常组织（如肾足细胞，睾丸，卵巢，乳腺等）表达，但在各型 …

2017年11月2日 · Our trial demonstrated that WT1-specific TCR-T cells that were produced by ex vivo culture of polyclonal peripheral T cells survived in vivo and retained the capacity to mount immune responses to WT1, and that they further provided transient antileukemic effects in patients with refractory AML.

2019年11月13日 · We have shown that the WT1-TCR T cells demonstrated a strong safety profile without detectable on-target, off-tumour toxicity and no severe adverse events in the ten patients treated. An important cause of treatment failure for adoptive cellular therapies is the lack of persistence of transferred T cells leading to loss of disease specific effects.

2024年8月12日 · 在儿童AML骨髓微环境3D模型中验证 eTCR-/- WT1-TCR的细胞毒性 总之， 本项研究利用WT1-TCR替代了脐带血来源的CD8 T细胞的内源TCR，并在体外对该TCR-T cells ...

Here we isolated an HLA-A*0201 restricted WT1 reactive T cell receptor (TCR) by stimulating PBL of healthy donors with the peptide WT1:126-134 in vitro. This TCR mediated peptide recognition down to a concentration of ~0.1 ng/ml when pulsed onto T2 cells as well as recognition of HLA-A*0201+ target cells transfected with full-length WT1 cDNA.

Resulting WT1-specific TCR-T cells exhibited high efficacy in killing primary AML from bone marrow and ALL tumor-bearing NOD SCID gamma mice . The treatment of these mice with genetically modified WT1-specific TCR-T cells significantly reduced tumor growth and enhanced survival without inducing GVHD ( 37 ).

The WT1 protein is an attractive target for immunotherapy of leukemia and solid cancer since elevated expression has been demonstrated in AML, CML, MDS and in breast, colon and ovarian cancer. In the past, we have isolated high avidity CTL specific for a WT1-derived peptide presented by HLA-A2 and cloned the TCR alpha and beta genes of a WT1 ...

2024年10月30日 · 2017年，【Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS】创建了一种针对WT1肽的TCR-T细胞。 重要的是，这种TCR只能在HLA-A*24:02的背景下识别WT1肽，因此患者选择受到限制。

2017年11月2日 · Our trial demonstrated that WT1-specific TCR-T cells that were produced by ex vivo culture of polyclonal peripheral T cells survived in vivo and retained the capacity to mount immune responses to WT1, and that they further provided transient antileukemic effects in patients with refractory AML.

2020年12月19日 · Greenberg团队尝试在造血干细胞治疗后，平行进行WT1 TCR-T细胞回输治疗，评价其能否降低复发率。 12名受试者进行了T细胞回输，后续跟踪回访时间长达44个月，均未发生肿瘤复发，与之相比，对照组的复发率为46%。

Donor-derived, EBV-specific CD8 + T cells engineered to express a high-affinity WT1-specific TCR established persistent T cell responses that safely prevented post-HCT relapse in patients with high-risk AML.

2011年8月11日 · To address this problem, we have recently established a novel retroviral vector system encoding siRNAs for endogenous TCR genes (siTCR vector). In this study, to test the clinical application of siTCR gene therapy for human leukemia, we examined in detail the efficacy and safety of WT1- siTCR –transduced T cells.

Wilms tumor 1 (WT1) is an intracellular tumor-associated antigen that remains inaccessible to antibodies. Recently, T-cell receptor (TCR) mimic antibodies (TCRm-Abs), which recognize peptides loaded on human leukocyte antigen (HLA) with higher specificity and affinity than TCR, have been developed a …

2024年8月10日 · 首先，该文章通过CRISPR/Cas9系统敲除内源TCR，接着通过慢病毒转导的方式整合W1-TCR的α chain和β chain，使得CD8+ T细胞成功表达WT1-TCR，最终产生eTCR-/- WT1-TCR-T cells（图1）。 图1. eTCR-/- WT1-TCR-T cells 生产流程图. 接着，作者对比了eTCR-/- WT1-TCR and eTCR+/+ WT1-TCR T cell的免疫学表型。 它们具有相似的CD45RA和CD62L细胞分群，有相似memory marker表达。 其次，激活marker和抑制marker表达类似，只有CD127 …

2022年2月9日 · A unique WT1 37-45-specific TCR showed antigen-specific responses and efficiently killed AML blasts, acute lymphoblastic leukemia blasts, and glioblastoma cells in vitro and in vivo in the absence of off-tumor toxicity. T cells engineered to express this receptor are being advanced into clinical development for AML immunotherapy and represent a ...