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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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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...
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Extraction of Tissue Antigens for Functional Assays
08:32

Extraction of Tissue Antigens for Functional Assays

Published on: September 10, 2012

假肢抗原受体

Jingjing Shen1, Daniel A Vallera1, Carston R Wagner1

  • 1†Departments of Medicinal Chemistry and ‡Therapeutic Radiology, University of Minnesota, 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.

Journal of the American Chemical Society
|August 1, 2015
PubMed
概括

化学自组装纳米环 (CSAN) 为癌症免疫疗法提供了一种新方法,作为假体抗原受体. 这些双特异性CSAN针对T细胞和恶性B细胞,触发免疫反应,同时允许安全的药物诱导分解.

科学领域:

  • 免疫学
  • 生物技术
  • 癌症学

背景情况:

  • 化学抗原受体 (CAR) 对癌症免疫疗法具有前景,但由于T细胞基因工程,它们面临生产和安全挑战.
  • 现有的CAR T细胞疗法需要对患者的T细胞进行复杂的基因改造,这在制造和安全协议方面构成了重大障碍.

研究的目的:

  • 开发一种用于癌症免疫治疗的新型非基因工程假体抗原受体系统.
  • 评估化学自组装纳米环 (CSAN) 作为T细胞参与和向癌细胞的双特异性结合剂的有效性和安全性.

主要方法:

  • 化学自组装纳米环 (CSAN) 设计以显示单链抗体,针对T细胞上的CD3 ε子单元和恶性B细胞上的CD22抗原.
  • 随着时间的推移,对抗CD3/抗CD22 CSANs的结合稳定性进行了评估.
  • 使用trimethoprim证明了CSANs从细胞膜中分解.
  • 在存在CD22+癌细胞的情况下测量了T细胞激活标志物 (IL-2,IFN-γ产生) 和细胞毒性.

主要成果:

  • 抗CD3/抗CD22的CSAN与T细胞表面结合时间超过4天.
  • 通过使用trimethoprim,可以有效和安全地从T细胞中分解CSAN.
  • 用CSAN修改的T细胞显示有选择性的IL-2和IFN-γ产生,并对CD22+B细胞产生细胞毒性.

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结论:

  • 双特异性CSAN代表了癌症免疫疗法的非基因工程替代品.
  • CSAN提供了一个潜在的更安全和更容易生产的平台,用于对抗B细胞恶性瘤的T细胞.
  • 这种三甲胺诱导的拆解机制为这种假肢抗原受体系统提供了可控制的安全功能.