肿瘤细胞治疗研究
英文原题：Regulatable C-X-C chemokine receptor type 4 in iPSC-derived NK cells improves bone marrow chemotaxis and targeting resident tumor.
iPSC来源的NK 细胞（iNKs）已成为一种有前景的细胞疗法，尤其对于难治或复发性急性髓系白血病（R/R AML）患者，但针对iNKs趋化性的研究有限。
iPSC来源的NK 细胞（iNKs）已成为一种有前景的细胞疗法，尤其对于难治性或复发性急性髓系白血病（R/R AML）患者，但针对iNKs趋化性的研究有限。在此，我们证明C-X-C趋化因子受体4型（CXCR4）在iNKs中显著降低，导致骨髓（BM）浸润受损，而由于CXCR4诱导的分化失败，iPSC中组成型表达的CXCR4无法挽救这一缺陷。为解决此问题，我们开发了一种策略，允许在iNK成熟阶段特异性表达CXCR4，而不损害最终iNK产量和功能。工程化iNKs表现出增强的BM浸润，从而在AML小鼠模型中改善了治疗效果。这引起了对iNK趋化性的关注，提供了一种通过将精心设计的基因编辑与干细胞相结合用于细胞产品开发的有意义策略，并获得了用于AML治疗的改进的有效NK细胞。
iPSC-derived natural killer cells (iNKs) have emerged as a promising cellular therapy, especially for the refractory or relapsed acute myeloid leukemia (R/R AML) patients, but limited research focused on the chemotaxis of iNKs. Here we demonstrate that C-X-C chemokine receptor type 4 (CXCR4) is significantly reduced in iNKs, resulting in impaired bone marrow (BM) infiltration, which cannot be rescued by constitutively expressed CXCR4 in iPSC due to CXCR4-induced differentiation failure. To address this, we developed a strategy to allow specific expression of CXCR4 during the iNK maturation stage without compromising the final iNK yield and function. The engineered iNKs exhibited enhanced BM infiltration, resulting in improved therapeutic effects in AML murine models. This, brought attention to iNK chemotaxis, provided a meaningful strategy by incorporating well-designed gene editing with stem cells for cell product development, and obtained improved effective NK cells for AML therapy.
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