尽管急性髓系白血病（AML）治疗取得了相当大的进展，但异基因造血干细胞移植（HSCT）后复发仍然频繁，且预后不良。复发已被证明与 HSCT 之前 CD34+ 白血病干细胞的不完全根除有关。此前，我们已经证明，一种新型 CD34 导向的双特异性 T 细胞接合器 (BTE) 可以有效地将 T 细胞效应功能重定向到癌细胞，从而在体外和体内消除白血病细胞。然而，它对 γδ T 细胞的影响仍不清楚。在这项研究中，我们使用体外扩增的 γδ T 细胞作为效应器测试了 CD34 特异性 BTE 的功效。我们发现 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，γδ T 细胞介导的杀伤作用优于 αβ T 细胞介导的细胞毒性。此外，我们观察到只有在 BTE 存在的情况下，γδ T 细胞才能在体外诱导原发性 AML 母细胞杀伤。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)，也不裂解健康骨髓样本中的 CD34 HSC。© 2024 作者。经泰勒许可出版

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 CD34intermediate endothelial blood-brain barrier cell line (hCMEC/D3) nor lysed CD34+ HSCs from healthy bone marrow samples.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.