Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple Myeloma: An Evolving Therapeutic Strategy

C. Chung
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引用次数: 27

Abstract

Multiple myeloma (referred to henceforth as myeloma) is a B‐cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor. Accordingly, a need exists for new therapeutic avenues that can overcome resistance to current therapies and improve survival outcomes. In addition, myeloma is associated with progressive immune dysregulation, with defects in T‐cell immunity, natural killer cell function, and the antigen‐presenting capacity of dendritic cells, resulting in a tumor microenvironment that promotes disease tolerance and progression. Together, the immunosuppressive microenvironment and oncogenic mutations activate signaling networks that promote myeloma cell survival. Immunotherapy incorporates novel treatment options (e.g., monoclonal antibodies, antibody‐drug conjugates, chimeric antigen receptor T‐cell therapy, immune checkpoint inhibitors, bispecific antibodies, and tumor vaccines) either alone or in combination with existing lines of therapies (e.g., immunomodulatory agents, proteasome inhibitors, and histone deacetylase inhibitors) to enhance the host anti myeloma immunity within the bone marrow microenvironment and improve clinical response. Following the U.S. Food and Drug Administration approval of daratumumab and elotuzumab in 2015, more immunotherapeutic agents are expected to be become available as valuable treatment options in the near future. This review provides a basic understanding of the role of immunotherapy in modulating the bone marrow tumor microenvironment and its role in the treatment of myeloma. Clinical efficacy and safety of recently approved therapeutic monoclonal antibodies (daratumumab, elotuzumab) are discussed, along with the therapeutic potential of emerging immunotherapies (antibody‐drug conjugates, chimeric antigen receptor T‐cell therapy, tumor vaccines, and immune checkpoint inhibitors).
免疫疗法在多发性骨髓瘤中靶向骨髓微环境的作用:一种不断发展的治疗策略
多发性骨髓瘤(以下简称骨髓瘤)是一种B细胞恶性肿瘤,其特征是骨髓浆细胞生长不正常。在过去的十年中,骨髓瘤的治疗模式经历了重大的演变,随着对疾病发病机制的理解的提高,以及治疗药物的发展,不仅针对肿瘤细胞,而且针对其微环境。尽管有这些治疗进展,复发或难治性骨髓瘤患者的预后仍然很差。因此,需要新的治疗途径来克服对当前疗法的耐药性并改善生存结果。此外,骨髓瘤与进行性免疫失调、T细胞免疫、自然杀伤细胞功能和树突状细胞抗原呈递能力缺陷有关,导致肿瘤微环境促进疾病耐受性和进展。免疫抑制微环境和致癌突变共同激活促进骨髓瘤细胞存活的信号网络。免疫疗法结合了新的治疗选择(如单克隆抗体、抗体-药物偶联物、嵌合抗原受体T细胞疗法、免疫检查点抑制剂、双特异性抗体和肿瘤疫苗),可以单独使用,也可以与现有的治疗方法(如免疫调节剂、蛋白酶体抑制剂和组蛋白去乙酰化酶抑制剂)联合使用,以增强宿主在骨髓微环境中的抗骨髓瘤免疫,改善临床反应。继2015年美国食品和药物管理局批准了daratumumab和elotuzumab之后,预计在不久的将来会有更多的免疫治疗药物作为有价值的治疗选择。本文综述了免疫治疗在调节骨髓肿瘤微环境中的作用及其在骨髓瘤治疗中的作用。讨论了最近批准的治疗性单克隆抗体(daratumumab, elotuzumab)的临床疗效和安全性,以及新兴免疫疗法(抗体-药物偶联物,嵌合抗原受体T细胞疗法,肿瘤疫苗和免疫检查点抑制剂)的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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