肿瘤细胞治疗研究
英文原题：Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells.
Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells.
我们的结果表明，γδ T细胞既不靶向健康的CD34中间型内皮血脑屏障细胞系（hCMEC/D3），也不裂解来自健康骨髓样本的CD34+ HSC。
尽管急性髓系白血病（AML）的治疗取得了相当大的进展，异基因造血干细胞移植（HSCT）后复发仍然频繁，且与不良预后相关。已表明复发与HSCT前CD34+白血病干细胞清除不完全相关。此前，我们已经表明，一种新型靶向CD34的双特异性T细胞衔接器（BTE）能够有效地将T细胞效应功能重定向至癌细胞，从而在体外和体内消除白血病细胞。然而，其对γδ T细胞的影响仍不清楚。在本研究中，我们使用体外扩增的γδ T细胞作为效应细胞，测试了CD34特异性BTE的疗效。我们表明，BTE与γδ T细胞和CD34+白血病细胞系结合，并以剂量依赖性方式诱导靶细胞杀伤。此外，发现γδ T细胞介导的杀伤优于αβ T细胞介导的细胞毒性。此外，我们观察到，仅在BTE存在的情况下，γδ T细胞在体外诱导原代AML原始细胞杀伤。重要的是，我们的结果表明，γδ T细胞既不靶向健康的CD34中间内皮血脑屏障细胞系（hCMEC/D3），也不裂解来自健康骨髓样本的CD34+ HSC。
Despite the considerable progress in acute myeloid leukemia (AML) treatment, relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is still frequent and associated with a poor prognosis. Relapse has been shown to be correlated with an incomplete eradication of CD34+ leukemic stem cells prior to HSCT. Previously, we have shown that a novel CD34-directed, bispecific T-cell engager (BTE) can efficiently redirect the T-cell effector function toward cancer cells, thus eliminating leukemic cells in vitro and in vivo . However, its impact on γδ T-cells is still unclear. In this study, we tested the efficacy of the CD34-specific BTE using in vitro expanded γδ T-cells as effectors. We showed that the BTEs bind to γδ T-cells and CD34+ leukemic cell lines and induce target cell killing in a dose-dependent manner. Additionally, γδ T-cell mediated killing was found to be superior to αβ T-cell mediated cytotoxicity. Furthermore, we observed that only in the presence of BTE the γδ T-cells induced primary AML blast killing in vitro . Importantly, our results show that γδ T-cells did not target the healthy CD34 intermediate endothelial blood-brain barrier cell line (hCMEC/D3) nor lysed CD34+ HSCs from healthy bone marrow samples.
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