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装载 IL-2 融合蛋白提高 CAR-T 细胞适应性及抗实体瘤疗效

英文原题:Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.

查看英文原题

Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.

PubMed 2024/04/06(内容时间) Biochim Biophys Acta Mol Basis Dis Q1 · IF 5(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法是一种强效免疫疗法,通过诱导抗原特异性免疫应答,已在血液系统恶性肿瘤治疗中取得重大成功。然而,对于具有免疫抑制性微环境的实体瘤,CAR-T 细胞疗法缓解率仍有限。联合工程化策略正推动相关方法发展,以克服免疫抑制屏障并增强抗肿瘤应答。本研究构建了一种共工程化IL-2突变体CAR-T 细胞,以增强CAR-T 细胞对抗实体瘤的能力并有效抑制肿瘤。我们使CAR-T 细胞同时表达靶向肿瘤抗原的CAR和突变型人白细胞介素2(IL-2m),从而增强CAR-T 细胞体外适应性、重塑免疫排斥型肿瘤微环境、提高CAR-T 细胞在实体瘤中的浸润,并改善肿瘤控制,且未见显著全身毒性。总体而言,本研究展示了一种通用的CAR-T 细胞武装策略,可用于开发和优化对抗实体瘤的CAR-T 细胞。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses.

However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses.

Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors.

We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity.

Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors.

论文信息

作者
Li S、Xia Y、Hou R、Wang X、Zhao X、Guan Z、Ma W、Xu Y
第一作者单位
Cancer Institute, Xuzhou Medical University, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, China.China
通讯作者单位
Cancer Institute, Xuzhou Medical University, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, China. Electronic address: sm200@sohu.com.China
文献类型
非美国政府资助研究
期刊
Biochimica et biophysica acta. Molecular basis of disease2024 Jun
原文标识
PubMed 38583815 · DOI 10.1016/j.bbadis.2024.167159