Baselga J, Mendelsohn J
Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Pharmacol Ther. 1994 Oct;64(1):127-54. doi: 10.1016/0163-7258(94)90036-1.
Human tumors express high levels of growth factors and their receptors, and many types of malignant cells appear to exhibit autocrine- or paracrine-stimulated growth. Therefore, antireceptor directed therapies have the potential of being useful anti-cancer agents. A series of murine monoclonal antibodies (MAbs) directed against human growth factor receptors and their corresponding growth factors have been produced. MAbs against the receptors for epidermal growth factor, Her2/Neu, transferrin, insulin-like growth factor, interleukin, (IL)-2 and IL-1 are currently being evaluated. MAbs directed against epidermal growth factor, transforming growth factor-alpha, bombesin, IL-2, and IL-6 also are under study. These MAbs have shown promising preclinical activity, and some of them are being tested in clinical trials. So far, anti-tumor responses have been observed with anti-IL-2 receptor, anti-bombesin and anti-IL-6 MAbs. Further research is focusing in the production of "chimeric" and "humanized" MAbs, in order to obviate the problem of host immune reactions.
人类肿瘤表达高水平的生长因子及其受体,许多类型的恶性细胞似乎表现出自分泌或旁分泌刺激的生长。因此,抗受体导向疗法有潜力成为有用的抗癌药物。已经产生了一系列针对人类生长因子受体及其相应生长因子的鼠单克隆抗体(MAb)。目前正在评估针对表皮生长因子、Her2/Neu、转铁蛋白、胰岛素样生长因子、白细胞介素(IL)-2和IL-1受体的单克隆抗体。针对表皮生长因子、转化生长因子-α、蛙皮素、IL-2和IL-6的单克隆抗体也在研究中。这些单克隆抗体已显示出有前景的临床前活性,其中一些正在进行临床试验。到目前为止,已观察到抗IL-2受体、抗蛙皮素和抗IL-6单克隆抗体的抗肿瘤反应。进一步的研究集中在“嵌合”和“人源化”单克隆抗体的生产上,以避免宿主免疫反应问题。