ImClone Systems Corporation, 33 ImClone Drive, Branchburg, NJ 08876, USA.
Cancer. 2010 Feb 15;116(4 Suppl):1018-26. doi: 10.1002/cncr.24788.
A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies.
大量证据表明，血小板衍生生长因子（PDGF）家族及其相关受体是肿瘤治疗开发的潜在靶点，因为它们在各种癌症的增殖和存活以及肿瘤基质和血管的调节和生长中起着关键作用。有几种非特异性靶向 PDGF 信号轴的小分子目前被用作抗癌疗法或正在开发中。然而，对于这些药物中的大多数来说，PDGF 和其受体既不是抗癌活性的主要靶点，也不是主要的介导物。IMC-3G3 是一种完全人源化的免疫球蛋白 G1 亚类单克隆抗体，与人 PDGF 受体α（PDGFRα）具有高亲和力特异性结合，阻断 PDGF 配体结合和 PDGFRα 激活。临床前研究结果以及 PDGFRα 在许多类型的癌症和癌症相关基质中的频繁表达支持了 IMC-3G3 的临床开发的基本原理。目前，正在早期临床开发中评估 IMC-3G3 在几种实体恶性肿瘤患者中的应用。
