Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Department of Immunology, China Basic Medical Theory of Chinese Medicine, Academy of Chinese Medical Sciences, Beijing 100700, P.R. China.
Oncol Rep. 2018 Mar;39(3):1245-1252. doi: 10.3892/or.2018.6211. Epub 2018 Jan 11.
In the present study, we aimed to investigate whether EGFR or HER2 may serve as a target for T cell-mediated immunotherapy against human bladder cancer. Expression of EGFR and HER2 was detected on the surface of bladder cancer cells, including Pumc-91 and T24 cells, and their chemotherapeutic drug-resistant counterparts. Activated T cells (ATCs) were generated from healthy PBMCs that were stimulated by the combination of anti-CD3 monoclonal antibody and anti‑CD28 monoclonal antibody in the presence of interleukin-2 for 14 days. The ATCs were then armed with chemically hetero-conjugated anti-CD3xanti-EGFR (EGFRBi-Ab) or anti-CD3xanti-HER2 (HER2Bi-Ab). The specific cytolytic activity of ATCs armed with EGFRBi-Ab or HER2Bi-Ab against human bladder cancer cells was evaluated by lactate dehydrogenase activity assays in vitro. In contrast to unarmed ATCs, EGFRBi-Ab-armed ATCs and HER2Bi-Ab-armed ATCs showed increased cytotoxic activity against bladder cancer cells. Moreover, Bi-Ab-armed ATCs expressed higher levels of activating marker CD69 and secreted more IFN-γ, TNF-α and IL-2 than did unarmed ATCs. EGFRBi-Ab- or HER2Bi-Ab-armed ATCs may provide a promising immunotherapy for bladder cancer.
在本研究中，我们旨在探讨 EGFR 或 HER2 是否可作为针对人类膀胱癌的 T 细胞介导免疫疗法的靶标。我们检测了 EGFR 和 HER2 在膀胱癌细胞表面的表达，包括 Pumc-91 和 T24 细胞及其化疗耐药对应物。从健康的 PBMC 中生成活化的 T 细胞 (ATCs)，这些细胞在存在白细胞介素-2 的情况下，通过抗-CD3 单克隆抗体和抗-CD28 单克隆抗体的组合刺激 14 天而产生。然后，用化学异质偶联的抗-CD3x抗-EGFR (EGFRBi-Ab) 或抗-CD3x抗-HER2 (HER2Bi-Ab) 武装 ATCs。通过体外乳酸脱氢酶活性测定评估 EGFRBi-Ab 或 HER2Bi-Ab 武装的 ATCs 对人膀胱癌细胞的特异性细胞毒性活性。与未武装的 ATCs 相比，EGFRBi-Ab 武装的 ATCs 和 HER2Bi-Ab 武装的 ATCs 对膀胱癌细胞表现出增强的细胞毒性活性。此外，Bi-Ab 武装的 ATCs 表达更高水平的激活标记物 CD69 并分泌更多的 IFN-γ、TNF-α 和 IL-2，高于未武装的 ATCs。EGFRBi-Ab 或 HER2Bi-Ab 武装的 ATCs 可能为膀胱癌提供一种有前途的免疫疗法。
