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靶向 BCMA 的 CAR-T 细胞在多发性骨髓瘤细胞系中患者与健康供者间的细胞毒性与耗竭标志物

英文原题:Cytotoxicity and exhaustion markers of chimeric antigen receptor T cells targeting BCMA in multiple myeloma cell lines between patients and healthy donors.

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Cytotoxicity and exhaustion markers of chimeric antigen receptor T cells targeting BCMA in multiple myeloma cell lines between patients and healthy donors.

PubMed 2023/05/24(内容时间) Eur J Haematol Q2 · IF 2.6(JCR 2025)

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研究概要

我们的 BCMA CAR-T 细胞主要为效应/效应记忆细胞,可在体外清除表达 BCMA 的细胞,且不同细胞群体间的耗竭标志物水平相似。

中文摘要

多发性骨髓瘤(MM)占血液系统恶性肿瘤的 10%,但多数患者会复发/难治。我们希望利用现有平台拓展 CAR-T 细胞疗法治疗 MM。

为志愿者或 MM 患者制备 BCMA CAR-T 淋巴细胞。使用 ddPCR 检测转导效率,通过流式细胞术监测免疫表型和耗竭标志物。将 BCMA CAR-T 与 BCMA CAR 或 Mock T 细胞共培养,并与阳性和阴性靶细胞 K562/hBCMA-ECTM 和 K562 共培养,测试其疗效。

成功从同意参与的志愿者或 MM 患者制备 BCMA CAR-T 细胞;其 CAR BCMA 表达平均分别为每个细胞 4.07±1.95 和 4.65±1.21 个拷贝。改造后的 T 细胞主要为效应记忆 T 细胞。BCMA CAR-T 细胞可特异性清除 K562/hBCMA-ECTM 细胞系,而 K562 细胞系存活。有趣的是,BCMA CAR、Mock T 细胞和 MM 患者 PBMC 表达相似水平的耗竭标志物 TIM-3、LAG-3 和 PD-1。

本研究的 BCMA CAR-T 细胞主要属于效应/效应记忆表型,可在体外清除 BCMA 表达细胞;不同细胞群体间耗竭标志物水平相似。

展开英文摘要原文

Multiple myeloma (MM) accounts for 10% of hematologic malignancies. However, most of the patients suffered from relapsed/refractory disease. We would like to expand CAR T cell therapy to treat MM using our current platform.

BCMA CAR T lymphocytes were generated for volunteers or MM patients. The transduction efficiency was detected by the ddPCR technique. Immunophenotyping and exhaustion markers were monitored by flow cytometry. The efficacy of BCMA CAR T cells was tested using coculturing with BCMA CAR or mock, and the positive and negative targets, K562/hBCMA-ECTM and K562, respectively.

BCMA CAR T cells were generated from consented volunteers or MM patients and could be detected CAR BCMA expression at a mean of 4.07 1.95 or 4.65 1.21 copies/cell, respectively. Those modified T cells were primarily effector memory T cells. Our BCMA CAR T cells could explicitly eradicate the K562/hBCMA-ECTM cell line while the K562 cell line survived. Interestingly, the BCMA CAR, mock T cells, and peripheral blood mononuclear cells from MM patients expressed similar levels of the exhaustion makers, TIM-3, LAG-3, and PD1.

Our BCMA CAR T cells, mainly effector/effector memory, could eliminate BCMA-expressing cells in vitro and had similar levels of exhaustion markers among different populations.

论文信息

作者
Prasongtanakij S、Preedagasamzin S、Jittorntrum B、Anurathapan U、Puavilai T、Niparuck P、Chantrathammachart P、Piyajaroenkij T
第一作者单位
Research, Academics and Innovation Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Thailand
通讯作者单位
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.Thailand
期刊
European journal of haematology2024 Feb
原文标识
PubMed 37222081 · DOI 10.1111/ejh.14007