CD19/CD20双向的仿真抗原受体工程自然杀手细胞对急性淋巴细胞白血病的细胞毒性有所改善
Na Yang1,2, Caili Zhang1, Yingchun Zhang3
1Tissue Engineering and Stem Cell Experiment Center, Guizhou Medical University (GMU), Guiyang, Guizhou, China.
Journal of translational medicine
|March 13, 2024
概括
开发针对CD19和CD20抗原的双向化学抗原受体自然杀手 (CAR-NK) 细胞提高了疗效,并防止瘤在急性淋巴细胞白血病 (ALL) 中脱离. 这些CAR-NK细胞显示出潜在的ALL治疗的更好的向和安全性.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 在瘤学瘤学.
背景情况:
- 化学抗原受体自然杀手 (CAR-NK) 细胞在CAR细胞疗法中表现有前途,但在抗原逃逸方面面临挑战.
- 以前的研究表明,由于抗原下调,CAR-NK细胞努力消除CD19+拉吉细胞.
- 瘤复发的风险来自目标抗原逃逸需要改进的CAR-NK细胞策略.
研究的目的:
- 为了增强CD19 CAR-NK细胞对抗CD19表达瘤的疗效.
- 通过解决目标抗原逃逸,减轻瘤复发风险.
- 开发CD19和CD20双向的CAR-NK细胞,以改善ALL治疗.
主要方法:
- 通过体外转录编码编码抗CD19和抗CD20CAR的构造mRNA.
- 通过将CAR mRNA电转移到UCB-NK细胞中,生成CD19/CD20双向CAR-NK细胞.
- 通过流细胞计和ELISA评估双CAR表达,细胞毒性和细胞因子释放.
主要成果:
- 在电解后的NK细胞上达到86.4%的双CAR表达,持续表达长达96小时.
- 与单个向的CAR-NK细胞相比,双重向的CAR-NK细胞对ALL细胞系的特定细胞毒性有所增加.
- 观察到高水平的穿孔素,IFN-γ和IL-15,以及像CD69.9这样的激活标志物的高表达.
结论:
- CD19/CD20双向CAR-NK细胞有效地解决ALL中的抗原异质性,降低瘤逃逸风险.
- 这些工程细胞为ALL提供高效和安全的"现成"治疗产品.
- 这项研究为在ALL治疗中应用双重向的CAR-NK细胞提供了基础.
关键词:
急性淋巴细胞白血病 (Acute Lymphoblastic Leukemia) 是一种急性淋巴细胞白血病.化学抗原受体的化学抗原受体双重目标是双重的目标.自然杀手细胞是自然杀手细胞.它们是mRNARNA.更多相关视频
06:08Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model
Published on: February 10, 2023
1.3K
12:16A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
14.7K
相关概念视频
02:57Targeted Cancer Therapies
7.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.6K
01:27Cytotoxic T Cells-mediated Immune Response
907
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
907