Ren Hui, Li Jun, Liu Jing-Jing, Guo Hui-Ling, Jiang Tao
Department of General Surgery, the Second Hospital, Jilin University, Changchun, China.
Asian Pac J Cancer Prev. 2012;13(6):2795-8. doi: 10.7314/apjcp.2012.13.6.2795.
This study is conducted to evaluate the effects of anti-HER-2 anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells.
Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2 CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors.
Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2 CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2 CD3 BsAb case. The growth of xenografts with HER2 CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05).
HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2 anti-CD3 BsAb exerting clear anti-tumor effects.
本研究旨在评估抗HER-2抗CD3双特异性抗体(BsAb)对HER-2/neu过表达的人结肠癌细胞的作用。
将HCT-116细胞分别暴露于赫赛汀、抗CD3抗体和BsAb抗体后,通过MTT法评估细胞生长情况。应用免疫细胞化学方法检测HCT-116细胞的HER-2水平。在裸鼠模型中,将HER-2 CD3 BsAb与效应细胞(正常人外周血淋巴细胞)联合使用,观察肿瘤的体内生长情况。
与对照组相比,使用效应细胞联合抗CD3单克隆抗体、赫赛汀或HER2 CD3 BsAb时,体外和体内肿瘤细胞生长均受到显著抑制(P<0.05),其中以HER2 CD3 BsAb组最为明显。与抗CD3单克隆抗体或赫赛汀组相比,HER2 CD3 BsAb联合效应细胞的异种移植瘤生长也受到显著抑制(P<0.05)。
HER-2/neu可能是结直肠癌免疫治疗的一个有用靶点,抗HER2抗CD3 BsAb具有明显的抗肿瘤作用。