Mercatelli Daniele, Bortolotti Massimo, Bazzocchi Alberto, Bolognesi Andrea, Polito Letizia
Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Department of Diagnostic and Interventional Radiology, The "Rizzoli" Orthopaedic Institute, Via G. C. Pupilli 1, 40136 Bologna, Italy.
Biomedicines. 2018 Feb 10;6(1):19. doi: 10.3390/biomedicines6010019.
Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new therapeutic approaches have been evaluated, mainly immunotherapy with antibody-drug conjugates or immunoconjugates. These molecules consist of a carrier (frequently an antibody) joined by a linker to a toxic moiety (drug, radionuclide, or toxin). Although several clinical trials with immunoconjugates have been conducted, mainly in hematological tumors, their potential as therapeutic agents is relatively under-explored in many types of cancer. In this review, we report the immunoconjugates directed against OS surface antigens, considering the in vitro and in vivo studies. To date, several attempts have been made in preclinical settings, reporting encouraging results and demonstrating the validity of the idea. The clinical experience with glembatumumab vedotin may provide new insights into the real efficacy of antibody-drug conjugates for OS therapy, possibly giving more information about patient selection. Moreover, new opportunities could arise from the ongoing clinical trials in OS patients with unconjugated antibodies that could represent future candidates as carrier moieties of immunoconjugates.
骨肉瘤（OS）是一种具有侵袭性的间充质来源的骨样生成肿瘤，是最常见的原发性骨恶性肿瘤。其病因复杂且常常不明。目前高级别骨肉瘤治疗的标准方案是新辅助化疗，随后进行手术及术后化疗。为了提高患者生存率，人们评估了新的治疗方法，主要是抗体-药物偶联物或免疫偶联物的免疫疗法。这些分子由载体（通常是抗体）通过连接子与毒性部分（药物、放射性核素或毒素）相连组成。尽管已经开展了多项免疫偶联物的临床试验，主要针对血液系统肿瘤，但在多种癌症类型中，其作为治疗药物的潜力仍相对未得到充分探索。在本综述中，我们结合体外和体内研究，报告针对骨肉瘤表面抗原的免疫偶联物。迄今为止，在临床前研究中已进行了多次尝试，取得了令人鼓舞的结果，并证明了该理念的有效性。glembatumumab vedotin的临床经验可能为抗体-药物偶联物治疗骨肉瘤的实际疗效提供新见解，或许能提供更多关于患者选择的信息。此外，正在进行的针对骨肉瘤患者的未偶联抗体临床试验可能会带来新机遇，这些抗体可能成为免疫偶联物载体部分的未来候选者。
