工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
NECTIN-4 重定向的 T 细胞抗原耦合器 T 细胞携带 CD28 对实体瘤表现出更优的抗肿瘤反应
英文原题：NECTIN-4-redirected T cell Antigen Coupler T cells bearing CD28 show superior antitumor responses against solid tumors.
查看英文原题
NECTIN-4-redirected T cell Antigen Coupler T cells bearing CD28 show superior antitumor responses against solid tumors.
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研究概要
我们的数据突出表明，NECTIN-4 TAC28-T 细胞可能是一种有前景、安全且有效的细胞疗法，用于治疗 NECTIN-4 过表达的实体瘤。
研究思路结论见上方概要
背景
T细胞抗原偶联器（TAC）T细胞利用内源性T细胞受体（TCR）的所有信号亚基来触发T细胞活化和肿瘤细胞裂解，且细胞因子释放极少。实体瘤细胞免疫治疗的一些主要障碍包括细胞向肿瘤的浸润效率低下、缺乏长期的细胞持久性以及治疗相关毒性。
方法
为增强TAC-T细胞对实体瘤的细胞毒性潜力，我们构建了一种新型NECTIN-4靶向TAC-T变体——NECTIN-4 TAC28-T，其整合了共刺激CD28胞质区，并在体外和体内比较了NECTIN-4 TAC-T细胞与NECTIN-4 TAC28-T细胞的抗肿瘤活性。
结果
我们证明了NECTIN-4 TAC28-T细胞可被NECTIN-4蛋白包被的磁珠（NECTIN-4-beads）有效激活，并进一步揭示整合的CD28共刺激结构域增强了其激活和增殖能力。值得注意的是，NECTIN-4 TAC28-T细胞在体外和体内均比原始的NECTIN-4 TAC-T细胞表现出更好的抗肿瘤效果。
展开英文摘要原文
METHODS
To boost the cytotoxic potential of TAC-T cells against solid tumors, we generated a novel NECTIN-4-targeted TAC-T variant, NECTIN-4 TAC28-T, which integrated the co-stimulatory CD28 cytoplasmic region, and compared the anti-tumor activities between NECTIN-4 TAC-T cells and NECTIN-4 TAC28-T cells in vitro and vivo.
RESULTS
We demonstrated NECTIN-4 TAC28-Tcells could be effectively activated by NECTIN-4 protein-coated magnetic beads (NECTIN-4-beads), and further revealed that the incorporated CD28 co-stimulatory domain enhanced their activation and proliferation capabilities. Notably, NECTIN-4 TAC28-T cells exhibited better anti-tumor effects both in vitro and in vivo than the original NECTIN-4 TAC-T cells. DISCUSSION: Our data highlighted that NECTIN-4 TAC28-T cells may represent a promising, safe and effective cell therapy for NECTIN-4-overexpressing solid tumors.
论文信息
- 作者
- Wei C、Huang X、Xu T、Fang Y、Wang F、He Q、Zhang P、Yu Q
- 第一作者单位
- Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.China
- 通讯作者单位
- Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, Zhejiang, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2024
- 原文标识
- PubMed 39735536 · DOI 10.3389/fimmu.2024.1456443
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