相同信号、不同命运，CD28 CAR-T和4-1BB CAR-T的差异根源
cd28和4-1bb是现在car-t使用最多的两种共刺激因子。 越来越多的研究显示，二者产生的CAR-T细胞表型，效应水平及存留时间有明显差异。 全球众多顶级的细胞治疗研究中心，做了大量研究，寻找二者差异的根源。
A comparison of chimeric antigen receptors containing CD28 ... - Nature
2021年7月6日 · Currently, the costimulatory receptors CD28 and 4-1BB are the only source of costimulatory domains used in commercial CAR T cell products. Herein, we provide an overview of CD28 and 4-1BB...
CD28 vs 4-1BB | 孰优孰劣？ - 知乎专栏
CD28和4-1BB在T细胞活化中的扮演着重要作用，这些共刺激分子的信号结构域可以整合到CAR中，以增强CAR-T细胞的功能、增殖和治疗功效。 CARs上的共刺激结构域. CARs于1991年首次被描述，当时三个不同的研究小组证明，通过将CD4、CD8或IL-2受体α亚单位 (IL-2Rα) 的细胞外部分连接到TCR复合物的CD3ζ的胞质结构域的嵌合构建体上时，可以重现TCR信号传导。 随后，研究人员用抗体衍生的scFv 取代这些CARs的细胞外部分，以指导T细胞对抗所需的靶抗原； 第一 …
CD28 hinge used in chimeric antigen receptor (CAR) T-cells …
2024年8月31日 · CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic...
Chimeric antigen receptor signaling: Functional ... - Science
2020年5月20日 · Most studies of CAR signaling show that CD28-containing CARs signal more rapidly and intensely than 4-1BB–containing CARs at early time points, using a variety of readouts (15, 36, 37, 41, 51). Specific evaluation of proximal signaling pathways also indicates that signal transducer and activator of transcription 3 (STAT3) and PI3K appear to ...
CD28 CAR T Cells for the Treatment of T Cell Malignancies
2023年11月2日 · We analyzed specific CAR activity against CD28 expressing T-ALL cell lines after retroviral transduction into primary human T cells. Additional CD28 knockout (KO) by CRISPR/Cas9 could prevent T cell fratricide.
CD28 is superior to 4-1BB costimulation in generating CAR-NK …
2025年3月3日 · This study compared two dominant CAR designs used in T cells—CD28-CD3ζ (28z) and 4-1BB-CD3ζ (BBz)—and found that CD28 costimulation offers superior functionality in NK cells. 28z CAR-NK cells exhibited significantly better activation, cytotoxicity, and in vivo anti-tumor efficacy than BBz CAR-NK cells, with similar persistence and tumor ...
Synergistic T cell signaling by 41BB and CD28 is optimally …
Second generation (2G) chimeric antigen receptors (CARs) contain a CD28 or 41BB co-stimulatory endodomain and elicit remarkable efficacy in hematological malignancies. Third generation (3G) CARs extend this linear blueprint by fusing both co-stimulatory units in series.
CD28-CAR-T cell activation through FYN kinase signaling ... - Cell …
2023年2月21日 · Wu et al. discover that LCK, an essential kinase for TCR signaling, is dispensable for CAR signaling. CD28 domain and the kinase FYN mediate this LCK-independent signaling. LCK-disrupted CAR-T shows increased in vivo anti-tumor efficacy—attributed to the improved memory/persistence and reduced exhaustion—and the potential for allogeneic use.
施明、郑骏年团队在Frontiers in Immunology发表文章：系统论述基于CD28共刺激分子的CAR …
5 天之前 · 在cd28信号基序优化方面，突变ymnm、prrp和pyap基序可降低t细胞耗竭和功能障碍，增强car-t细胞的持久性和抗肿瘤功效；分离cd28与cd3ζ信号，设计双靶car-t，可增强对双阳性肿瘤细胞的反应性，降低脱靶及肿瘤抗原逃逸风险；将cd28与其他共刺激分子组合，包括串联 ...