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
用于体内 AML 靶向的 scFv 鉴定与 CAR-T 细胞生成整合策略
英文原题：Integrated scFv identification and CAR T cell generation for AML targeting in vivo.
查看英文原题
Integrated scFv identification and CAR T cell generation for AML targeting in vivo.
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中文摘要
癌症免疫治疗取得显著进展，嵌合抗原受体（CAR）T细胞疗法的发展尤为突出。本研究整合单链可变片段（scFv）研发与CAR-T 细胞制备，采用新开发的scFv噬菌粒文库。高通量PacBio长读长测序在所建文库中鉴定出4.5×10^7种独特全长scFv蛋白。作为原理验证，研究者筛选靶向C型凝集素样分子1（CLL1）的scFv，并将其克隆至第三代逆转录病毒CAR骨架中。功能实验显示，这些CAR-T 细胞可在体外特异且有效地靶向CLL1阳性AML细胞。体内研究显示，与对照相比，肿瘤负荷降低、生存率提高。总之，筛选靶向CLL1的肿瘤特异性scFv，可快速制备能够在体内有效杀伤肿瘤的AML特异性CAR-T 细胞。
展开英文摘要原文
Cancer immunotherapy has witnessed remarkable advancements, particularly in the development of chimeric antigen receptor (CAR) T cell therapy.
Here, we integrated single chain variable fragment (scFv) development with CAR T cell generation based on a newly developed scFv phagemid library. High-throughput long-read PacBio sequencing identified 4. 5 10 7 unique full-length scFv proteins within the generated library. As a proof of principle, we screened for scFvs targeting C-type lectin-like molecule-1 (CLL1) with subsequent cloning into a third generation retroviral CAR backbone.
Functional assays revealed the specificity and potency of these CAR T cells in targeting CLL1-positive AML cells in vitro. In vivo studies reduced tumor burden and improved survival rates compared to controls. Taken together, screening for tumor-specific scFvs against CLL1 can rapidly generate AML-specific CAR T cells with effective tumor killing in vivo.
论文信息
- 作者
- Liu Y、Lauk A、Sedloev D、Brysting J、Cetin E、Liu C、Mönnig M、Luft T
- 单位
- Medical Faculty Heidelberg and Department of Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.Germany
- 期刊
- International journal of cancer2026 Feb 15
- 原文标识
- PubMed 41037684 · DOI 10.1002/ijc.70146
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