IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy

IF 3.2 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Cytotherapy Pub Date : 2024-11-01 Epub Date: 2024-06-06 DOI:10.1016/j.jcyt.2024.06.001

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Abstract

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.

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IL-27 工程化 CAR.19-NK-92 细胞显示出更强的疗效

自然杀伤（NK）细胞的嵌合抗原受体（CAR）工程在早期临床研究中取得了可喜的成果。然而，提高 CAR-NK 细胞的疗效势在必行。在本研究中，我们研究了共表达 IL-27 的第四代 CD19 靶向 CAR（CAR.19）对 NK-92 细胞的影响。我们观察到，在体外和异种移植小鼠 B 细胞淋巴瘤模型中，NK-92 细胞的增殖和对 B 细胞癌细胞株的细胞毒活性都有明显改善。我们对活化的 NK-92 CAR 变体进行的系统转录组分析进一步证明了 IL-27 在第四代 CAR 中的潜力，它能提供重要的生长和活化信号，从而克服基于 NK 细胞的肿瘤靶向疗法的局限性。将IL-27整合到CAR-NK细胞中是一种很有前景的策略，可以增强其治疗潜力，并对癌细胞产生强有力的反应。这些发现极大地丰富了第四代 CAR 工程在推动基于 NK 细胞的免疫疗法方面的潜力。

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来源期刊

Cytotherapy 医学-生物工程与应用微生物

CiteScore

6.30

自引率

4.40%

发文量

683

审稿时长

49 days

期刊介绍： The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.