工程B细胞表达完全可定制的抗体,具有增强的Fc功能.
Chun Huang1, Atishay Mathur1, Chan-Hua Chang1
1Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Research square
|September 18, 2025
概括
基因组编辑重新编程B细胞以创建定制的重链仅抗体 (HCAbs). 这种多功能平台允许定制抗体功能,半衰期和结构,以提高治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物技术是生物技术.
背景情况:
- B细胞自然产生对免疫反应至关重要的抗体.
- 抗体工程旨在提高治疗疗效和特异性.
- 目前的抗体疗法在效应器功能和半衰期方面存在局限性.
研究的目的:
- 为了设计B细胞以生产定制的重链抗体 (HCAbs).
- 探索免疫球蛋白重链局部 (IGH) 编辑平台的灵活性.
- 增强抗体效应器功能,延长半衰期,控制抗体结构.
主要方法:
- 在IGH常数区域内利用基因组编辑重新编程B细胞.
- 工程细胞表达表面B细胞受体 (BCR) 和分泌的HCAb异型.
- 引入了特定的突变来定制Fc域,强制执行同质化,并添加C端域.
主要成果:
- 成功地重新编程B细胞以表达具有自定义识别域的功能HCAbs.
- 证明了修改Fc域的能力,以增强效应器功能和延长半衰期.
- 实现了强制性HCAb同质化,防止了与内源性抗体链的不必要配对.
- 在秘密的HCAbs中展示了额外的C端域的安置和优先表达.
结论:
- HCAb编辑平台为创建完全定制的抗体分子提供了显著的灵活性.
- 可以利用工程B细胞产生具有量身定制性质的治疗抗体.
- 这种方法提供了一个强大的工具,通过利用B细胞生物学来推进基于抗体的疗法.
相关概念视频
B Cell Activation and Differentiation
16.1K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
16.1K
Special Features of Adaptive Immunity
2.9K
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,...
2.9K
Diversity of Antigen Receptors
1.4K
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...
1.4K
Antibody Structure
65.3K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.3K
Hybridoma Technology
17.3K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
17.3K
Antibody Structure and Classes
8.3K
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
8.3K


