Waldmann Thomas A, Morris John C
Metabolism Branch, Center for Cancer Research, National Cancer Institute NIH, Bethesda, Maryland 20892, USA.
Adv Immunol. 2006;90:83-131. doi: 10.1016/S0065-2776(06)90003-0.
Monoclonal antibodies are among the most rapidly expanding class of therapeutics for cancer treatment. Monoclonal antibodies targeting non-Hodgkin's lymphoma (NHL), Her-2/neu highly expressing metastatic breast cancer, colorectal cancer, acute myelogenous leukemia, and B-cell chronic lymphocytic leukemia (CLL) have received FDA approval. Promising new targets for antibody therapy include cellular growth factor receptors, mediators of tumor-driven neo-angiogenesis, as well as host negative immunoregulatory checkpoints that impede an effective immune response to neoplasia. Antibody efficacy has been increased by genetic engineering to humanize the antibodies and to increase their effector functions including antibody dependent cellular cytotoxicity. Furthermore, antibodies have been armed with cytokines, chemotherapeutic agents, toxins, and radionuclides to augment their efficacy as tumor cytotoxic agents. As a consequence of these advances, 30 years after their first development, monoclonal antibodies have become an important standard approach for the therapy of neoplasia with 19 therapeutic monoclonal antibodies now approved by the FDA including 8 for the treatment of cancer.
单克隆抗体是癌症治疗中发展最为迅速的一类治疗药物。靶向非霍奇金淋巴瘤（NHL）、高表达Her-2/neu的转移性乳腺癌、结直肠癌、急性髓性白血病和B细胞慢性淋巴细胞白血病（CLL）的单克隆抗体已获得美国食品药品监督管理局（FDA）批准。抗体治疗有前景的新靶点包括细胞生长因子受体、肿瘤驱动的新生血管生成介质，以及阻碍对肿瘤产生有效免疫反应的宿主负性免疫调节检查点。通过基因工程使抗体人源化并增强其效应功能（包括抗体依赖性细胞毒性），提高了抗体的疗效。此外，抗体还与细胞因子、化疗药物、毒素和放射性核素结合，以增强其作为肿瘤细胞毒性药物的疗效。由于这些进展，在首次研发30年后，单克隆抗体已成为肿瘤治疗的重要标准方法，目前FDA已批准19种治疗性单克隆抗体，其中8种用于癌症治疗。
