Center for the Study of Drug Development, Tufts University School of Medicine, 75 Kneeland Street, Suite 1100, Boston, MA 02111, USA.
Drug Discov Today. 2012 Sep;17(17-18):954-63. doi: 10.1016/j.drudis.2012.04.006. Epub 2012 Apr 26.
Targeted therapeutics such as monoclonal antibodies (mAbs) have proven successful as cancer drugs. To profile products that could be marketed in the future, we examined the current commercial clinical pipeline of mAb candidates for cancer. Our analysis revealed trends toward development of a variety of noncanonical mAbs, including antibody-drug conjugates (ADCs), bispecific antibodies, engineered antibodies and antibody fragments and/or domains. We found substantial diversity in the antibody sequence source, isotype, carbohydrate residues, targets and mechanisms of action (MOA). Although well-validated targets, such as epidermal growth factor receptor (EGFR) and CD20, continue to provide opportunities for companies, we found notable trends toward targeting less-well-validated antigens and exploration of innovative MOA such as the generation of anticancer immune responses or recruitment of cytotoxic T cells.
靶向治疗药物,如单克隆抗体(mAbs),已被证明是成功的癌症药物。为了分析未来可能上市的产品,我们研究了当前处于临床开发阶段的 mAb 候选药物,用于癌症治疗。我们的分析揭示了开发各种非典型 mAb 的趋势,包括抗体药物偶联物(ADCs)、双特异性抗体、工程化抗体以及抗体片段和/或结构域。我们发现抗体序列来源、同种型、糖基化残基、靶点和作用机制(MOA)存在显著的多样性。虽然表皮生长因子受体(EGFR)和 CD20 等经过充分验证的靶点仍然为公司提供了机会,但我们发现,针对验证程度较低的抗原的趋势明显,并且正在探索创新的 MOA,如产生抗癌免疫反应或募集细胞毒性 T 细胞。