-scFv抗原识别域有效地赋予CAR T细胞多抗原特异性
Jaquelyn T Zoine1, Kalyan Immadisetty2, Jorge Ibanez-Vega1
1Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell reports. Medicine
|February 13, 2024
概括
这项研究提出了一种新的双特异性嵌合抗原受体 (CAR) T细胞治疗策略,以克服急性髓性白血病 (AML) 中的免疫逃逸. 双重向的CAR有效地消除了表达GRP78或CD123的癌细胞,从而提高了治疗效率.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 免疫逃脱是化学抗原受体 (CAR) T细胞疗法在急性髓性白血病 (AML) 等血液恶性瘤中的一个主要挑战.
- 针对多个抗原可以潜在地克服瘤异质性,并防止免疫逃逸.
研究的目的:
- 开发和验证针对GRP78和CD123抗原的双特异性CAR T细胞策略,以提高AML的疗效.
- 调查链接器变异对-scFv双特异CARs功能的影响.
主要方法:
- 通过结合GRP78特异性和CD123特异性scFv使用各种链接器,构建了一个双特异性的CAR T细胞结构 (78.123).
- 进行了双特异性CAR T细胞的免疫类型和功能特征.
- 利用蛋白质结构预测来分析链接器对CAR功能的影响.
主要成果:
- 双特异性CAR T细胞成功地识别并杀死表达GRP78,CD123或两者的瘤细胞.
- 与双特异性CAR T细胞相比,当两种抗原都存在时,与单特异性对应物相比,观察到较好的抗瘤活性.
- 连接器的长度和灵活性被确定为影响双特定CAR功能的关键因素.
结论:
- 一种针对GRP78和CD123的新型双特异性CAR设计策略可以有效地打击AML中的免疫逃逸.
- 这种方法提供了一种有希望的策略,以提高CAR T细胞治疗对血液恶性瘤的疗效.
- -scFv双特异性CAR设计可适应针对其他抗原组合.
相关概念视频
01:22T Cell Activation and Clonal Selection
733
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
733
01:28Diversity of Antigen Receptors
589
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
589
01:26Antigens Involved in Adaptive Immunity
493
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
493
01:20Special Features of Adaptive Immunity
820
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
820
00:42Cross-reactivity
31.1K
Overview
31.1K
01:22Antigen Presenting Cells
1.8K
The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
1.8K