Department of Structural and Functional Biology, University of Naples Federico II, I-80126 Naples, Italy.
Oncol Rep. 2012 Jul;28(1):297-302. doi: 10.3892/or.2012.1760. Epub 2012 Apr 10.
Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor environment, thus promoting androgen-independent cell growth. The consequent development of hormone refractory tumors is a major obstacle in prostate cancer therapy. The inhibition of ErbB2 signal transduction pathways by the use of human antibodies could be a valuable alternative strategy for cancer therapy. We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4. Thus, Erb-hcAb could be a promising candidate in the immunotherapy of prostate cancer for which no obvious treatment has been reported so far.
在发达国家,前列腺癌是男性最常见的恶性肿瘤。表皮生长因子受体 2(ErbB2)是一种在许多人类癌症类型中过表达的酪氨酸激酶受体,它在雄激素缺乏的环境中通过激活雄激素受体促进前列腺癌细胞的生长,从而促进雄激素非依赖性细胞生长。激素难治性肿瘤的随后发展是前列腺癌治疗的主要障碍。使用人源抗体抑制 ErbB2 信号转导途径可能是癌症治疗的一种有价值的替代策略。我们在体外和体内对三种针对 ErbB2 不同表位的不同抗体的抗肿瘤作用进行了比较分析:赫赛汀(曲妥珠单抗)、2C4(帕妥珠单抗)和 Erb-hcAb(人抗 ErbB2 紧凑型抗体),这是我们实验室生产的一种新型全人源紧凑型抗体。在此,我们证明 Erb-hcAb 能有效抑制雄激素依赖性和非依赖性前列腺癌细胞的生长。与赫赛汀或 2C4 相比,Erb-hcAb 对一些细胞系的抗肿瘤作用更为有效。因此,Erb-hcAb 可能是一种很有前途的候选药物,可用于目前尚无明显治疗方法的前列腺癌的免疫治疗。