von Mehren M, Weiner L M
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Curr Opin Oncol. 1996 Nov;8(6):493-8. doi: 10.1097/00001622-199611000-00009.
Monoclonal antibodies have been developed for cancer therapy because they specifically target tumor-related antigens. The current design of antibodies and delivery strategies seeks to overcome the obstacles encountered in delivering antibodies to their targets. Protein engineering techniques to humanize murine antibodies diminishes the immune response, which develops against murine monoclonal antibodies, allowing for multiple doses. Antibodies linked to vasoactive substances or conjugated to liposomes increase antibody and drug localization to tumors. Altering the sizes of antibodies and the methods by which they are conjugated to radioactive isotopes have delineated methods to increase efficacy and decrease toxicity. Tumor growth factors increasingly are being targeted by antibody-based therapeutics. To enhance immune activation of cytotoxic effector cells, bispecific antibodies and antibodies linked to superantigens are being examined. Prodrugs are being converted to their active compounds at the tumor site by antibodies conjugated to enzymes. Finally, intrabodies which can bind to intracellular proteins and are important for the malignant phenotype of the cell, are being developed.
单克隆抗体已被开发用于癌症治疗，因为它们能特异性地靶向肿瘤相关抗原。当前抗体的设计和递送策略旨在克服将抗体递送至其靶点时遇到的障碍。使鼠源抗体人源化的蛋白质工程技术减少了针对鼠源单克隆抗体产生的免疫反应，从而可以多次给药。与血管活性物质相连或与脂质体偶联的抗体可增加抗体和药物在肿瘤中的定位。改变抗体大小以及将它们与放射性同位素偶联的方法已明确了提高疗效和降低毒性的方法。基于抗体的治疗越来越多地靶向肿瘤生长因子。为增强细胞毒性效应细胞的免疫激活，正在研究双特异性抗体和与超抗原相连的抗体。通过与酶偶联的抗体，前体药物在肿瘤部位被转化为其活性化合物。最后，正在开发能够结合细胞内蛋白质且对细胞恶性表型很重要的细胞内抗体。
