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免疫疗法:多发性骨髓瘤治疗新时代。

Immunotherapy: A Novel Era of Promising Treatments for Multiple Myeloma.

机构信息

Department of Hematology, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain.

Josep Carreras Leukaemia Research Institute, Barcelona, Spain.

出版信息

Int J Mol Sci. 2018 Nov 15;19(11):3613. doi: 10.3390/ijms19113613.

Abstract

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by clonal proliferation of malignant plasma cells in bone marrow. In the last 20 years, the introduction of autologous stem cell transplantation, followed by proteasome inhibitors and immunomodulatory agents, increased the survival of MM patients by 50%. However, still a high proportion of patients relapse and become refractory, especially, high-risk patients with adverse cytogenetics where these treatment combinations have shown limited benefit. Therefore, novel strategies, such as immunotherapy, have been developed in the last few years to help improve the survival of these patients. Immunotherapy treatments include a high number of different strategies used to attack the tumor cells by using the immune system. Here, we will review the most successful immunotherapy strategies published up to date in patients with relapsed or refractory (R/R) MM, including monoclonal antibodies targeting specific antigens on the tumor cells, antibodies combined with cytotoxic drugs or Antibodies Drug Conjugates, immune checkpoint inhibitors which eliminate the barriers that damper immune cells and prevent them from attacking tumor cells, bi-specific T-cell engagers antibodies (BiTEs), bi-specific antibodies and the infusion of chimeric antigen receptor-modified T cells. We overview the results of clinical studies that have been presented up to date and also review pre-clinical studies describing potential novel treatments for MM.

摘要

多发性骨髓瘤(MM)仍然是一种不可治愈的血液恶性肿瘤,其特征是骨髓中恶性浆细胞的克隆性增殖。在过去的 20 年中,自体干细胞移植的引入,随后是蛋白酶体抑制剂和免疫调节剂的引入,使 MM 患者的生存率提高了 50%。然而,仍然有很大比例的患者复发并变得耐药,特别是具有不良细胞遗传学的高危患者,这些治疗组合显示出有限的益处。因此,近年来开发了新的策略,如免疫疗法,以帮助改善这些患者的生存。免疫疗法治疗包括大量不同的策略,用于利用免疫系统攻击肿瘤细胞。在这里,我们将回顾迄今为止在复发或难治性(R/R)MM 患者中发表的最成功的免疫治疗策略,包括针对肿瘤细胞上特定抗原的单克隆抗体、与细胞毒性药物结合的抗体或抗体药物偶联物、免疫检查点抑制剂,这些抑制剂消除了抑制免疫细胞并阻止它们攻击肿瘤细胞的障碍,双特异性 T 细胞衔接抗体(BiTEs)、双特异性抗体和嵌合抗原受体修饰的 T 细胞输注。我们概述了迄今为止已提出的临床研究结果,并回顾了描述 MM 潜在新治疗方法的临床前研究。

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