Khodke Purva, Hasurkar Dhananjay, Upadhyay Aakanksha, Shedge Aditi, Sippy Rhea, Vasant Kumbhar Bajarang
Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) (Deemed-to-be University), Vile Parle (West), Mumbai, India.
School of Biosciences and Bioengineering, D Y Patil International University, Akurdi, Pune, India.
Int Rev Immunol. 2025 Jun 19:1-28. doi: 10.1080/08830185.2025.2515839.
B-cells are vital immune cells that differentiate into plasma cells to produce antibodies targeting specific antigens. They also act as Antigen Presenting Cells, displaying processed antigens on Major Histocompatibility Complex class-II molecules to activate helper T-cells. This process triggers immune response and memory development. B-cells have surface antigens crucial for their function, which are often overexpressed in B cell cancers, making them targets for therapies like Chimeric Antigen Receptor (CAR) T-cell therapy. However, the choice of antigen is crucial. Tumor associated antigens are common but can cause off-target effects, while tumor specific antigens are more specific but less common. Furthermore, the precise epitope on the antigen recognized by the CAR-T cells significantly influences activation, which can also depend on the epitope's distance from the B-cell membrane. To facilitate the identification of extracellular regions of tumor antigens for CAR interactions, this review models tumor antigen structures embedded in the lipid bilayer, analyzing their roles and functions. Specifically, the characterization of B-cell surface antigens, encompassing their structural features and their potential as targets for CAR-T therapy are discussed. Each antigen is meticulously examined to gain insights into their specific roles within B cell biology and their potential as therapeutic targets. In conclusion, this review highlights the importance of understanding B cell antigens for the development of effective CAR-T cell therapies. The insights into antigen structures and functions presented here can guide the selection of optimal targets and the design of CAR-T cells to combat B cell malignancies effectively.
B细胞是重要的免疫细胞,可分化为浆细胞以产生针对特定抗原的抗体。它们还作为抗原呈递细胞,在主要组织相容性复合体II类分子上展示加工后的抗原,以激活辅助性T细胞。这一过程触发免疫反应和记忆形成。B细胞具有对其功能至关重要的表面抗原,这些抗原在B细胞癌症中常常过度表达,使其成为嵌合抗原受体(CAR)T细胞疗法等治疗方法的靶点。然而,抗原的选择至关重要。肿瘤相关抗原很常见,但可能会导致脱靶效应,而肿瘤特异性抗原则更具特异性,但较为罕见。此外,CAR-T细胞识别的抗原上的确切表位对激活有显著影响,这也可能取决于表位与B细胞膜的距离。为便于识别用于CAR相互作用的肿瘤抗原的细胞外区域,本综述对嵌入脂质双层的肿瘤抗原结构进行建模,分析其作用和功能。具体而言,讨论了B细胞表面抗原的特征,包括其结构特征及其作为CAR-T疗法靶点的潜力。对每种抗原都进行了细致研究,以深入了解它们在B细胞生物学中的特定作用及其作为治疗靶点的潜力。总之,本综述强调了了解B细胞抗原对于开发有效的CAR-T细胞疗法的重要性。本文介绍的对抗原结构和功能的见解可指导最佳靶点的选择以及CAR-T细胞的设计,以有效对抗B细胞恶性肿瘤。
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