Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol, University, Bangkok, Thailand.
Bioengineered. 2022 Jun;13(6):14188-14203. doi: 10.1080/21655979.2022.2084262.
Adoptive cell transfer (ACT) is a promising approach for cancer treatment. Activation of T lymphocytes by elf-differentiated yeloid-derived ntigen-presenting-cells eactive against umor (SmartDC) resulted in specific anti-cancer function. Folate receptor alpha (FRα) is highly expressed in breast cancer (BC) cells and thus potential to be a target antigen for ACT. To explore the SmartDC technology for treatment of BC, we create SmartDC expressing FRα antigen (SmartDC-FRα) for activation of FRα-specific T lymphocytes. Human primary monocytes were transduced with lentiviruses containing tri-cistronic complementary DNA sequences encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and FRα to generate SmartDC-FRα. Autologous T lymphocytes were activated by SmartDC-FRα by coculture. The activated T lymphocytes exhibited enhanced cytotoxicity against FRα-expressing BC cell cultures. Up to 84.9 ± 6.2% of MDA-MB-231 and 89.7 ± 1.9% of MCF-7 BC cell lines were specifically lysed at an effector-to-target ratio of 20:1. The cytotoxicity of T lymphocytes activated by SmartDC-FRα was also demonstrated in three-dimensional (3D) spheroid culture of FRα-expressing BC cells marked by size reduction and spheroid disruption. This study thus portray the potential development of T lymphocytes activated by SmartDC-FRα as ACT in FRα-expressing BC treatment.
过继性细胞转移（ACT）是一种有前途的癌症治疗方法。通过分化的树突状细胞（SmartDC）激活 T 淋巴细胞，使其对肿瘤具有反应性，从而产生特异性的抗癌功能。叶酸受体 alpha（FRα）在乳腺癌（BC）细胞中高度表达，因此有可能成为 ACT 的靶抗原。为了探索 SmartDC 技术在 BC 治疗中的应用，我们构建了表达 FRα抗原的 SmartDC（SmartDC-FRα），以激活 FRα 特异性 T 淋巴细胞。用人原发性单核细胞转导含有编码粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素 4（IL-4）和 FRα 的三顺式 cDNA 序列的慢病毒，以生成 SmartDC-FRα。通过共培养将自体 T 淋巴细胞激活 SmartDC-FRα。激活的 T 淋巴细胞对表达 FRα 的 BC 细胞培养物显示出增强的细胞毒性。在效应物与靶标比例为 20:1 时，MDA-MB-231 和 MCF-7 BC 细胞系的特异性裂解率分别高达 84.9±6.2%和 89.7±1.9%。SmartDC-FRα 激活的 T 淋巴细胞在 FRα 表达的 BC 细胞的三维（3D）球体培养物中也显示出细胞毒性，表现为细胞体积缩小和球体破坏。因此，本研究描绘了 SmartDC-FRα 激活的 T 淋巴细胞作为 FRα 表达 BC 治疗中的 ACT 的潜在发展。
