针对CCR5-向的全基性玛-三角体CD19仿真抗原受体T细胞用于HIV相关的B细胞恶性病的免疫疗法
Ángel Ramírez-Fernández1,2,3,4,5, Alexander J Dimitri6,7,8,9,10, Fang Chen7
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. angel.ramirez-fernandez@pennmedicine.upenn.edu.
Nature biomedical engineering
|October 21, 2025
概括
这项研究提出了一种新方法,用于制造用于癌症治疗的现成的马-三角形 (γδ) CAR T 细胞. 这些工程 γδ CAR T 细胞显示出治疗B细胞恶性瘤的前景,即使在HIV阳性患者中也是如此.
科学领域:
- 免疫治疗是一种免疫疗法.
- 细胞疗法细胞疗法
- 在瘤学瘤学.
背景情况:
- 自主性CAR-T细胞是有效的,但成本昂贵,患者特异.
- 马-三角形 (γδ) T 细胞为全基 ("现成") 细胞疗法提供了潜力.
- γδ CAR T 细胞的临床使用受限于低频率,基因操纵挑战和分化问题.
研究的目的:
- 开发一种有效的方法来生产功能性,微分化的γδ CAR T 细胞.
- 为了设计具有对艾滋病毒等病毒感染的抗性增强的 γδ CAR T 细胞.
- 评估工程 γδ CAR T 细胞对抗B细胞恶性瘤的治疗潜力.
主要方法:
- 在体外激活和扩张周围血液的 γδ T 细胞.
- 利用人工抗原呈现细胞进行γδ T细胞扩张.
- 基因编辑将CD19 CAR插入CCR5位点,从而产生CCR5缺乏的γδ CAR T细胞 (γδ CCR5KI-CAR19).
主要成果:
- 在 γδ T 细胞中实现了高基因编辑率和高效的 CAR 集成.
- 产生微分化的,高功能的 γδ CAR T 细胞.
- 证明 γδ CCR5KI-CAR19 T 细胞对艾滋病毒具有抵抗力,并对B细胞淋巴瘤和白血病表现出强烈的抗瘤活性.
结论:
- 开发了一种可扩展的方法来产生强大的全基性γδ CAR T 细胞.
- γδ CCR5KI-CAR19 T细胞显示出治疗与HIV相关的B细胞恶性瘤的潜力.
- 这种方法支持大规模开发 γδ CAR T 细胞,用于各种免疫疗法.
更多相关视频
08:52Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
17.7K
09:56A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
1.3K
相关概念视频
01:27Tumor Immunotherapy
1.7K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
02:57Targeted Cancer Therapies
8.6K
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...
8.6K
01:27Cytotoxic T Cells-mediated Immune Response
6.5K
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...
6.5K