CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
新型抗 PD-1 抗体与表达 IL-7 的 CAR-T 细胞的整合增强对肺癌的靶向疗效
英文原题：Integration of a novel anti-PD-1 antibody with chimeric antigen receptor-T engineered to express interleukin-7 enhances targeting efficacy against lung cancer.
查看英文原题
Integration of a novel anti-PD-1 antibody with chimeric antigen receptor-T engineered to express interleukin-7 enhances targeting efficacy against lung cancer.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法已成为治疗血液系统恶性肿瘤的一种有前景的方法，但其在实体瘤中的疗效受到持久性有限的阻碍。为解决这一问题，免疫检查点抑制剂（ICIs）和细胞因子已被探索作为潜在的解决方案。在本研究中，我们开发了一种新型单克隆抗体（mAb）m8A8，它对人类PD-1具有高度特异性，并能有效破坏其与配体的相互作用。此外，我们工程化改造了CAR-T 细胞以表达人类IL-7，从而在异种移植模型中增强了抗肿瘤疗效。另外，源自m8A8的人鼠嵌合抗体C8A8被发现能显著增强IL-7工程化CAR-T 细胞的抗肿瘤活性。我们的发现为ICIs、细胞因子和CAR-T 细胞疗法在实体瘤治疗中的协同整合提供了有力证据和坚实依据。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising approach for hematological malignancies, yet its efficacy in solid tumors is hindered by limited persistence. To address this, immune checkpoint inhibitors (ICIs) and cytokines have been explored as potential solutions. In this study, we developed a novel monoclonal antibody (mAb), m8A8, which exhibits high specificity for human PD-1 and effectively disrupts its ligand interactions.
Furthermore, we engineered CAR-T cells to express human IL-7, resulting in enhanced anti-tumor efficacy in xenograft models.
Additionally, the human-mouse chimeric antibody C8A8, derived from m8A8, was found to significantly amplify the anti-tumor activity of IL-7-engineered CAR-T cells.
Our findings provide compelling evidence and a robust rationale for the synergistic integration of ICIs, cytokines, and CAR-T cell therapy in the treatment of solid tumors.
论文信息
- 作者
- Cheng C、Zhang L、Cao J、Li X、Wen Y、Liu K、Zhao T
- 单位
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.China
- 期刊
- Life medicine2025 Dec
- 原文标识
- PubMed 41450878 · DOI 10.1093/lifemedi/lnaf035
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