Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Curr Cancer Drug Targets. 2010 Mar;10(2):200-9. doi: 10.2174/156800910791054167.
In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as antibody therapy. Over the last 2 decades, several anti-GD2 antibodies have been developed. To reduce both the toxicity of the antibody and the development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that have progressively more human elements while at the same time reducing the mouse components. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with GD2-expressing tumors.
在开发针对高危癌症的新型免疫疗法的过程中，目标之一是寻找肿瘤靶点，这些靶点不会广泛存在于正常细胞中。一种这样的靶点是表面二唾液酸神经节苷脂 GD2。这种抗原存在于多种肿瘤表面，对于晚期疾病患者，这些肿瘤目前尚无治愈疗法。在儿童中，最常见的 GD2 表达肿瘤是神经母细胞瘤。GD2 也存在于其他几种高危肿瘤中，包括神经外胚层或上皮来源的肿瘤、几乎所有黑色素瘤以及约 50%的骨肉瘤和软组织肉瘤的肿瘤样本。由于该分子的肿瘤选择性表达，因此它是肿瘤特异性治疗（如抗体治疗）的一个有吸引力的靶点。在过去的 20 年中，已经开发了几种抗 GD2 抗体。为了降低抗体的毒性和人抗鼠抗体（HAMA）的产生，研究工作主要集中在探索具有逐渐更多人源成分的抗 GD2 抗体，同时减少鼠成分。本文将检查目前正在进行临床试验的抗体以及最近的进展，以改善表达 GD2 的肿瘤患者的抗体治疗。
