2. Academic Validation
  3. CD2 augmentation enhances CAR-T-cell efficacy via immunological synapse remodeling and T-cell exhaustion mitigation

CD2 augmentation enhances CAR-T-cell efficacy via immunological synapse remodeling and T-cell exhaustion mitigation

  • Cell Mol Immunol. 2025 Aug;22(8):935-948. doi: 10.1038/s41423-025-01314-6.
Qi Zhu # 1,  Jiajia Li # 1,  Nan Liu # 1,  Lu Han # 1,  Zhiqiang Wu 1,  Yao Wang 1,  Xin Lin 2 3 4,  Jianshu Wei 5,  Weidong Han 6
Affiliations

Affiliations

  • 1 Department of Biotherapy, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
  • 2 Changping Laboratory, Beijing, China. linxin307@tsinghua.edu.cn.
  • 3 School of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, China. linxin307@tsinghua.edu.cn.
  • 4 Tsinghua-Peking Center for Life Sciences, Beijing, China. linxin307@tsinghua.edu.cn.
  • 5 Changping Laboratory, Beijing, China. woshiwjs@hotmail.com.
  • 6 Department of Biotherapy, the First Medical Center, Chinese PLA General Hospital, Beijing, China. hanwdrsw@163.com.
  • # Contributed equally.
PMID: 40615696 DOI: 10.1038/s41423-025-01314-6
Abstract

CAR-T-cell therapy has made significant strides in treating hematological malignancies, yet its efficacy is often hampered by suboptimal T-cell functionality, marked by weak antitumor capabilities and a lack of durability. The immunological synapse, a key determinant of T-cell function, is influenced by the CD58-CD2 axis. The dynamic regulation of CD2 expression on T cells impacts the quality of CAR-mediated immunological synapses, affecting CAR-T-cell functional outcomes and differentiation. Our study demonstrated that CD2 expression levels are closely linked to the quality of immunological synapses formed by CAR-T cells and their antitumor potency. Exogenous CD2 supplementation enhances the ability of CAR-T cells to form high-quality synapses, reduces T-cell exhaustion, and increases sustained antitumor efficacy. Additionally, ectopic CD2 expression increases CAR-T-cell sensitivity to low-density antigens. Thus, replenishing CD2 in CAR-T cells is a promising strategy to increase the therapeutic efficacy of CAR-T-cell therapy.

Keywords

Antigen sensitivity; CAR-T cells; CD2, immunological synapse; T cell exhaustion.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z