肿瘤细胞治疗研究
英文原题：Lipid nanoparticle mediated delivery of Anti-CD19 CAR mRNA to umbilical cord blood NK cells for targeting CD19⁺ primary B-ALL cells.
嵌合抗原受体自然杀伤（CAR-NK）细胞疗法被认为是治疗血液系统恶性肿瘤，尤其是B细胞恶性肿瘤的一种有前景的方式。
嵌合抗原受体自然杀伤（CAR-NK）细胞疗法被认为是治疗血液系统恶性肿瘤，尤其是B细胞恶性肿瘤的一种有前景的方式。在本研究中，我们使用配制于专有可电离脂质纳米颗粒（LNP）中的抗CD19 CAR mRNA开发了“现货型”抗CD19 CAR-NK细胞。我们在体外评估了mRNA-LNP递送至脐带血（UCB）来源NK细胞和原代T细胞的效率，结果显示其在NK细胞中具有更优的递送效率。进一步研究表明，内吞机制中的巨胞饮可能在LNP高效转染NK细胞中发挥作用。尽管如此，通过该mRNA-LNP平台生成的CAR-NK细胞对CD19 + 靶细胞表现出显著增强的细胞毒性，例如EGFP + Raji稳定细胞系以及来源于难治/复发性B细胞急性淋巴细胞白血病（B-ALL）患者的原代恶性B细胞。这些发现凸显了mRNA-LNP平台在推进针对B细胞恶性肿瘤的CAR-NK疗法方面的前景。
Chimeric antigen receptor natural killer (CAR-NK) cell therapy is recognized as a promising modality for the treatment of hematologic malignancies, particularly B-cell malignancies. In this study, we developed "off-the-shelf" anti-CD19 CAR-NK cells using anti-CD19 CAR mRNAs formulated in proprietary ionizable lipid nanoparticles (LNPs). The efficiency of mRNA-LNP delivery into umbilical cord blood (UCB)-derived NK cells and primary T cells was evaluated in an in vitro setting, demonstrating superior delivery efficiency in NK cells. Further investigation showed a probable role for an endocytic mechanism, macropinocytosis, in efficient transfection of NK cells with LNPs. Nevertheless, CAR-NK cells generated through this mRNA-LNP platform exhibited significantly enhanced cytotoxicity against CD19 + target cells, such as EGFP + Raji stable cell line and primary malignant B cells derived from refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients. These findings highlight the promise of the mRNA-LNP platform in advancing CAR-NK therapies against B-cell malignancies.
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