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IL-27 工程化 CAR.19-NK-92 细胞表现出增强的治疗疗效

英文原题:IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.

查看英文原题

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

PubMed 2024/06/06(内容时间) Cytotherapy Q1 · IF 4.5(JCR 2025)

研究概要

自然杀伤(NK)细胞的嵌合抗原受体(CAR)工程化在早期临床研究中显示出有前景的结果。

中文摘要

CAR-NK细胞在早期临床研究中显示良好前景,但仍需进一步提高疗效。本研究考察在NK-92细胞中表达IL-27的第四代CD19 CAR。IL-27显著增强NK-92细胞对B细胞肿瘤细胞系的增殖和细胞毒作用,在体外及小鼠淋巴瘤异种移植模型中均有效。对活化CAR变体的系统转录组分析进一步支持IL-27可为第四代CAR提供关键生长和活化信号,克服NK细胞靶向治疗的局限。将IL-27整合进CAR-NK是增强治疗潜力、诱发强抗癌反应的有前景策略,为第四代CAR工程和NK细胞免疫疗法提供了证据。

展开英文摘要原文

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.

论文信息

作者
Biggi AFB、Silvestre RN、Tirapelle MC、de Azevedo JTC、García HDM、Henrique Dos Santos M、de Lima SCG、de Souza LEB
第一作者单位
Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.Brazil
通讯作者单位
Center for Cell-based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. Electronic address: virginia.picanco@hemocentro.fmrp.usp.br.Brazil
期刊
Cytotherapy2024 Nov
原文标识
PubMed 38970613 · DOI 10.1016/j.jcyt.2024.06.001