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.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
炎症触发型工程化巨噬细胞（MacTriggers）是治疗化疗耐药实体瘤的有前景的细胞疗法途径
英文原题：Inflammation-triggering Engineered Macrophages (MacTriggers) Are Promising Cell-based Therapeutic Avenues for Chemoresistant Solid Tumors.
查看英文原题
Inflammation-triggering Engineered Macrophages (MacTriggers) Are Promising Cell-based Therapeutic Avenues for Chemoresistant Solid Tumors.
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研究概要
MacTriggers 为化疗耐药的实体瘤提供了一种新颖、有效且更安全的治疗途径，解决了化疗的局限性并改善了耐药性癌症的预后。
研究思路结论见上方概要
背景
CAR-T 细胞疗法已显示出对化疗耐药的B细胞白血病和淋巴瘤的疗效，但在实体瘤中作用有限。本研究提出使用触发炎症的工程化巨噬细胞（MacTriggers）靶向化疗耐药肿瘤。静脉注射的MacTriggers浸润肿瘤，通过肿瘤坏死因子-α（TNF-α）诱导炎症，将免疫抑制微环境转化为免疫活跃状态，并增强抗肿瘤免疫应答。
方法
通过反复体内暴露于DOX，建立了DOX耐药的小鼠结肠癌细胞（DOX-Resi）。通过qPCR评估了WT或DOX-Resi细胞中Abcb1a（编码P-gp）的IC 50值和mRNA表达。MacTriggers被设计为在感知肿瘤相关精氨酸酶1（Arg1）活性后释放TNF-α。携带皮下DOX-Resi肿瘤的BALB/c小鼠接受了静脉注射MacTriggers或DOX。通过肿瘤体积监测、免疫组织化学和血清心肌肌钙蛋白-I测量，评估了肿瘤生长、组织学变化以及包括心脏毒性在内的副作用。
结果
DOX-Resi细胞的IC 50值约为WT细胞的2.5倍，Abcb1a表达显著更高。MacTriggers显著抑制了DOX-Resi肿瘤生长，而DOX疗效有限。MacTrigger给药未引起严重副作用，不同于DOX，后者诱导了心脏毒性。
展开英文摘要原文
MATERIALS AND METHODS
DOX-resistant murine colon cancer cells (DOX-Resi) were established by repeated in vivo exposure to DOX. IC 50 values and mRNA expression of Abcb1a (encoding P-gp) in WT or DOX-Resi cells were evaluated by qPCR. MacTriggers were engineered to release TNF-α upon sensing tumor-associated arginase 1 (Arg1) activity. BALB/c mice with subcutaneous DOX-Resi tumors received intravenous MacTriggers or DOX. Tumor growth, histological changes, and side effects, including cardiotoxicity, were assessed via tumor volume monitoring, immunohistochemistry, and serum cardiac troponin-I measurement.
RESULTS
DOX-Resi cells had an IC 50 value approximately 2.5 times higher than WT cells, with significantly higher Abcb1a expression. MacTriggers significantly suppressed DOX-Resi tumor growth, while DOX showed limited efficacy. MacTrigger administration did not cause severe side effects, unlike DOX, which induced cardiotoxicity.
CONCLUSION
MacTriggers offer a novel, effective, and safer therapeutic approach for chemoresistant solid tumors, addressing chemotherapy limitations and improving outcomes in drug-resistant cancers.
论文信息
- 作者
- Nii T、Yoshimi T、Tanito K、Hijii S、Takata H、Kishimura A、Mori T、Ishida T
- 第一作者单位
- Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan; nii.teruki.204@m.kyushu-u.ac.jp.Japan
- 通讯作者单位
- Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan; ykatatcm@mail.cstm.kyushu-u.ac.jp.Japan
- 期刊
- Anticancer research2025 Apr
- 原文标识
- PubMed 40155021 · DOI 10.21873/anticanres.17525