Ayed Ayed O, Chang Lung-Ji, Moreb Jan S
Department of Medicine, University of Florida, Gainesville, FL, USA.
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
Crit Rev Oncol Hematol. 2015 Dec;96(3):399-412. doi: 10.1016/j.critrevonc.2015.06.006. Epub 2015 Jun 28.
Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies and has been in the limelight of fast-track development of novel drugs that have contributed to the transformation of a rapidly lethal disease into a chronic illness with significant improvement in quality of life. Nonetheless, MM remains an incurable disease in many patients. Immunotherapy has been one of the approaches that had the highest hope for curing this disease. More than two decades of research and clinical trials in immunotherapy for MM have however resulted in very little impact on patient survival. The various immunotherapy approaches that have been attempted over the last two decades but were fraught with failure have already been extensively summarized in many published reviews. Nevertheless, in view of better understanding of the immune checkpoints, the innate immune system, and improved biotechnology, there is renewed hope. In this review, we will briefly discuss the unsuccessful approaches and emphasize the lessons learned, highlight the challenges that lie ahead, and discuss the more promising approaches, that already exist or being developed such as use of allogeneic stem cell transplants (allo-SCT) as a form of cellular immunotherapy, new monoclonal antibodies, chimeric antigen receptor (CAR) T-cell adoptive therapy, and NK cell therapy.
多发性骨髓瘤(MM)是一种浆细胞肿瘤,约占所有血液系统恶性肿瘤的10%,一直处于新型药物快速研发的关注焦点,这些药物已促使一种迅速致命的疾病转变为一种慢性疾病,患者生活质量得到显著改善。尽管如此,在许多患者中,MM仍然是一种无法治愈的疾病。免疫疗法一直是最有望治愈这种疾病的方法之一。然而,二十多年来针对MM的免疫疗法研究和临床试验对患者生存率的影响甚微。过去二十年来尝试的各种免疫疗法充满失败,许多已发表的综述对此已有广泛总结。尽管如此,鉴于对免疫检查点、固有免疫系统有了更好的理解,以及生物技术的进步,人们重燃希望。在本综述中,我们将简要讨论那些未成功的方法并强调从中吸取的教训,突出未来面临的挑战,并讨论已经存在或正在研发的更有前景的方法,如使用异基因干细胞移植(allo-SCT)作为一种细胞免疫疗法、新型单克隆抗体、嵌合抗原受体(CAR)T细胞过继性疗法和NK细胞疗法。