肿瘤细胞治疗研究
英文原题：Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia.
这些结果表明UCART123代表了一种针对AML的现成治疗方法。
急性髓系白血病（AML）是一种复发率高的疾病，其起源于白血病干细胞（LSCs）并由其维持。造血干细胞可通过一系列细胞表面抗原如 CD123 与 LSCs 区分开来，因此成为利用多种方法（包括 CAR T 细胞）消除 LSCs 的候选靶点。在此，我们评估了靶向 CD123 的同种异体基因编辑 CAR T 细胞（UCART123）消除 LSCs 的潜力。UCART123 细胞是使用 TALEN 基因编辑技术从健康供者中生成的 TCR 阴性 T 细胞，降低了移植物抗宿主病的可能性。作为安全性特征，细胞表达 RQR8 以允许通过利妥昔单抗消除。UCART123 在体外和体内有效消除 AML 细胞，在 AML 患者来源异种移植小鼠的总生存期方面具有显著获益。此外，UCART123 优先靶向 AML 而非正常细胞，对正常造血干/祖细胞具有适度毒性。总之，这些结果表明 UCART123 代表了一种用于 AML 的即用型治疗方法。
Acute myeloid leukemia (AML) is a disease with high incidence of relapse that is originated and maintained from leukemia stem cells (LSCs). Hematopoietic stem cells can be distinguished from LSCs by an array of cell surface antigens such as CD123, thus a candidate to eliminate LSCs using a variety of approaches, including CAR T cells. Here, we evaluate the potential of allogeneic gene-edited CAR T cells targeting CD123 to eliminate LSCs (UCART123). UCART123 cells are TCR neg T cells generated from healthy donors using TALEN gene-editing technology, decreasing the likelihood of graft vs host disease. As safety feature, cells express RQR8 to allow elimination with Rituximab. UCART123 effectively eliminates AML cells in vitro and in vivo with significant benefits in overall survival of AML-patient derived xenograft mice. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML.
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