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
以多胺为核心的血液代谢物组合预测大 B 细胞淋巴瘤 CAR-T 细胞治疗的不良应答
英文原题：A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma.
查看英文原题
A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma.
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中文摘要
抗CD19嵌合抗原受体（CAR）T细胞疗法治疗复发/难治性（r/r）大B细胞淋巴瘤（LBCL）仅在一部分患者中产生持久缓解。LBCL肿瘤中MYC过表达与治疗反应差相关。我们检验了MYC驱动的多胺特征作为液体活检是否能预测r/r LBCL患者对抗CD19 CAR-T 疗法的反应。血浆乙酰化多胺升高与非持久缓解相关。与此一致，调节乙酰化亚精胺水平的关键酶亚精胺合酶表达增加与r/r LBCL生存预后相关。广泛的代谢物筛选鉴定出更多标志物，最终形成由乙酰亚精胺、二乙酰亚精胺和溶血磷脂组成的6标志物组合（6MetP），并在来自另一机构的独立样本集中验证其可预测CAR-T 疗法非持久缓解。以多胺为中心的代谢组学液体活检组合对r/r LBCL患者CAR-T 疗法反应具有预测价值。
展开英文摘要原文
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory (r/r) large B cell lymphoma (LBCL) results in durable response in only a subset of patients. MYC overexpression in LBCL tumors is associated with poor response to treatment.
We tested whether an MYC-driven polyamine signature, as a liquid biopsy, is predictive of response to anti-CD19 CAR-T therapy in patients with r/r LBCL. Elevated plasma acetylated polyamines were associated with non-durable response. Concordantly, increased expression of spermidine synthase, a key enzyme that regulates levels of acetylated spermidine, was prognostic for survival in r/r LBCL.
A broad metabolite screen identified additional markers that resulted in a 6-marker panel (6MetP) consisting of acetylspermidine, diacetylspermidine, and lysophospholipids, which was validated in an independent set from another institution as predictive of non-durable response to CAR-T therapy. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in r/r LBCL.
论文信息
- 作者
- Fahrmann JF、Saini NY、Chia-Chi C、Irajizad E、Strati P、Nair R、Fayad LE、Ahmed S
- 第一作者单位
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.United States
- 通讯作者单位
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA. Electronic address: shanash@mdanderson.org.United States
- 文献类型
- 美国 NIH 资助研究
- 期刊
- Cell reports. Medicine2022 Nov 15
- 原文标识
- PubMed 36384092 · DOI 10.1016/j.xcrm.2022.100720
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