研究概要
SD-DC-BCMA 激活 T 细胞以进行抗原特异性肿瘤杀伤的能力,为过继性 T 细胞疗法在 MM 中的治疗应用提供了框架。
研究思路结论见上方概要
背景
B细胞成熟抗原(BCMA)是多发性骨髓瘤(MM)过继性T细胞治疗的理想靶点。在本研究中,我们评估了表达BCMA的自分化单核细胞衍生树突状细胞(SD-DC-BCMA)激活T细胞以杀伤MM细胞的效果。
方法
携带编码粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和BCMA三顺反子cDNA的慢病毒修饰SD-DC-BCMA被生成。评估了由SD-DC-BCMA激活的T细胞对MM细胞的细胞毒性。
结果
与未活化的T细胞或对照T细胞相比,经SD-DC-BCMA活化的T细胞对表达BCMA的MM细胞表现出剂量依赖性的细胞毒性,并产生高水平IFN-γ。在BCMA过表达细胞中,经SD-DC-BCMA活化的T细胞相比BCMA阴性细胞进一步显示出显著更高的杀伤能力。
展开英文摘要原文
MATERIALS AND METHODS
Lentivirus-modified SD-DC-BCMA harboring tri-cistronic cDNAs encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and BCMA was generated. Cytotoxicity of T cells activated by SD-DC-BCMA against MM cells was evaluated.
RESULTS
T cells activated by SD-DC-BCMA exhibited a dose-dependent cytotoxicity against BCMA-expressing MM cells and produced high IFN-γ levels, compared to inactivated T cells or control T cells. A significantly higher killing ability of T cells activated by SD-DC-BCMA was further demonstrated in BCMA-overexpressing cells when compared with BCMA-negative cells.
CONCLUSION
The potency of SD-DC-BCMA to activate T cells for antigen-specific cancer killing provides a framework for therapeutic application of adoptive T cell therapy in MM.
论文信息
- 作者
- Chiraphapphaiboon W、Luangwattananun P、Panya A、Jirapongwattana N、Punnakitikashem P、Chieochansin T、Junking M、Yenchitsomanus PT
- 第一作者单位
- International Graduate Program in Medical Biochemistry and Molecular Biology, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.Thailand
- 通讯作者单位
- Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; mutita.jun@mahidol.ac.th mjunking@gmail.com pathai.yen@mahidol.edu ptyench@gmail.com.Thailand
- 期刊
- Anticancer research2022 Apr