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CD19/CD22 双特异性嵌合抗原受体 NK-92 细胞的开发与评价

英文原题:CD19/CD22 bispecific chimeric antigen receptor‑NK‑92 cells are developed and evaluated.

PubMed 2023/04/19(内容时间) Oncol Lett Q3 · IF 2.1(JCR 2025)

研究概要

这些结果证明了抗CD19/CD22双特异性CAR-NK细胞的潜力,并表明优化NK细胞中的CAR结构可以提高CAR治疗的疗效。

中文摘要

抗CD19嵌合抗原受体(CAR)-T细胞已改善B细胞白血病和淋巴瘤患者的结局。然而,其应用和阳性结局仍然有限。CAR-T细胞目前受限于以自体血液作为其来源,并且其使用可导致CD19表达下调以及移植物抗宿主病和细胞因子释放综合征等并发症。本研究旨在使用来自鸡的抗CD22单克隆抗体克隆开发抗CD19/CD22双特异性CAR结构,并在自然杀伤(NK)-92细胞(一种人NK细胞系)中于体外和体内进行分析。通过靶细胞的存活评估抗CD19/CD22 CAR-NK-92细胞的细胞毒性,并使用流式细胞术计数。与其他CAR结构相比,抗CD22/CD19和环状结构的抗CD19/CD22双特异性CAR-NK-92细胞对OCI-Ly7细胞(一种人B细胞淋巴瘤细胞系)显示出改善的疗效。这些结果证明了抗CD19/CD22双特异性CAR-NK细胞的潜力,并表明优化NK细胞中的CAR结构可提高CAR治疗的疗效。

展开英文摘要原文

Anti-CD19 chimeric antigen receptor (CAR)-T cells have improved the outcomes of patients with B cell leukemia and lymphoma. However, their applications and positive outcomes remain limited. CAR-T cells are currently restricted to autologous blood as their source and their use can lead to downregulation of CD19 expression along with complications such as graft-versus-host disease and cytokine release syndrome. The present study aimed to develop anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyze them in natural killer (NK)-92 cells, a human NK cell line, in vitro and in vivo . Anti-CD19/CD22 CAR-NK-92 cell cytotoxicity was assessed by the survival of target cells and counted using flow cytometry. Anti-CD22/CD19 and loop-structured anti-CD19/CD22 bi-specific CAR-NK-92 cells showed improved efficacy against OCI-Ly7 cells, a human B cell lymphoma cell line, compared with other CAR structures. These results demonstrate the potential of anti-CD19/CD22 bispecific CAR-NK cells and suggested that optimizing CAR structures in NK cells can improve the efficacy of CAR therapy.

论文信息

作者
Kim H、Han M、Kim M、Kim H、Im HJ、Kim N、Koh KN
第一作者单位
Department of Convergence Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.South Korea
通讯作者单位
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.South Korea
期刊
Oncology letters2023 Jun
原文标识
PubMed 37153038 · DOI 10.3892/ol.2023.13822