International Graduate Program in Medical Biochemistry and Molecular Biology, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Anticancer Res. 2022 Apr;42(4):1785-1799. doi: 10.21873/anticanres.15655.
BACKGROUND/AIM: B cell maturation antigen (BCMA) is an ideal target for adoptive T cell therapy of multiple myeloma (MM). In this study, we evaluated self-differentiated monocyte-derived dendritic cells expressing BCMA (SD-DC-BCMA) to activate T cells for killing MM cells.
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.
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.
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.
背景/目的：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。在这项研究中，我们评估了表达 BCMA 的自分化单核细胞来源树突状细胞（SD-DC-BCMA），以激活 T 细胞杀伤 MM 细胞。
构建了携带编码粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-4（IL-4）和 BCMA 的三顺式 cDNA 的慢病毒修饰的 SD-DC-BCMA。评估了 SD-DC-BCMA 激活的 T 细胞对 MM 细胞的细胞毒性。
与失活 T 细胞或对照 T 细胞相比，SD-DC-BCMA 激活的 T 细胞对表达 BCMA 的 MM 细胞具有剂量依赖性细胞毒性，并产生高水平的 IFN-γ。与 BCMA 阴性细胞相比，SD-DC-BCMA 激活的 T 细胞对 BCMA 过表达细胞的杀伤能力显著提高。
SD-DC-BCMA 激活 T 细胞进行抗原特异性杀伤癌症的效力为 MM 中过继性 T 细胞治疗的治疗应用提供了框架。
