CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P. R. China.
PLoS One. 2013 Aug 27;8(8):e73261. doi: 10.1371/journal.pone.0073261. eCollection 2013.
Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.
抗 HER2/neu 抗体治疗已被报道可介导 HER2/neu(+)肿瘤的肿瘤消退。在这里，我们证明了 HER2 在广泛的人类黑色素瘤细胞中的表达，包括原代培养和七个细胞系，我们进一步研究了 HER2 是否可以作为人类黑色素瘤 T 细胞介导免疫治疗的靶标。通过荧光素酶报告基因产生的生物发光信号评估了用抗 CD3x 抗 HER2 双特异性抗体（HER2Bi-Ab）武装的激活 T 细胞（ATC）对 Malme-3M-luc 细胞的特异性细胞溶解活性，该报告基因不会改变 HER2 表达或 Malme-3M 细胞的增殖能力。与未武装的 ATC 相比，在效应物/靶标（E/T）比为 1:1、5:1 和 20:1 时，观察到 HER2Bi-武装的 ATC 对 Malme-3M-luc 细胞的细胞毒性活性增加。此外，在 E/T 比为 20:1 时，HER2Bi-武装的 ATC 表达更高水平的激活标志物 CD69 并分泌显著更高水平的 IFN-γ，而未武装的 ATC 相应水平更高。此外，与抗 HER2 mAb（赫赛汀®）或未武装的 ATC 相比，HER2Bi-武装的 ATC 对 Malme-3M-luc 肿瘤细胞显示出显著的抑制作用。此外，在黑色素瘤肿瘤细胞异种移植小鼠中，输注 HER2Bi-武装的 ATC 成功抑制了黑色素瘤肿瘤的生长。HER2Bi-武装的 ATC 的抗肿瘤作用可能为未来的黑色素瘤提供一种有前途的免疫治疗方法。
