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多发性骨髓瘤中的异基因干细胞移植:免疫疗法与新药

Allogeneic stem cell transplantation in multiple myeloma: immunotherapy and new drugs.

作者信息

Festuccia Moreno, Martino Massimo, Ferrando Federica, Messina Giuseppe, Moscato Tiziana, Fedele Roberta, Boccadoro Mario, Giaccone Luisa, Bruno Benedetto

机构信息

University of Torino, Presidio Molinette, and Department of Molecular Biotechnology and Health Sciences, Division of Hematology, A.O.U. Citta' della salute e della scienza di Torino, Presidio Molinette , Torino , Italy.

出版信息

Expert Opin Biol Ther. 2015 Jun;15(6):857-72. doi: 10.1517/14712598.2015.1036735. Epub 2015 Apr 12.

Abstract

INTRODUCTION

Autologous (auto) stem cell transplantation (SCT) and the development of new drugs have improved the survival of multiple myeloma (MM) patients. By contrast, though potentially curative, the use of allogeneic (allo)-SCT is controversial.

AREAS COVERED

A review has been conducted to examine the current evidence for the use of allo-SCT in MM. We have examined novel cell therapies that may be exploited to induce myeloma-specific immune responses including the new promising frontier of chimeric antigen receptor (CAR)-T and -natural killer (NK) cells.

EXPERT OPINION

One of the major controversies facing researchers in exploring the allo approach is the remarkable recent treatment improvement observed with second- and third-generation proteasome inhibitors and immunomodulatory drugs, monoclonal antibodies and deacetylase inhibitors. Despite these great advances, the disease remains to be incurable and allo-SCT may still play a role in the cure of MM. We think that allo-SCT conserves a role in MM and its curative potential in high-risk patients should be explored in the setting of control clinical trials. Novel cell therapies such as CAR technologies may open new avenues of research toward a potential cure. Data from currently ongoing prospective studies will be helpful to clarify pending clinical questions.

摘要

引言

自体干细胞移植(SCT)和新药的研发提高了多发性骨髓瘤(MM)患者的生存率。相比之下,尽管同种异体(allo)-SCT可能具有治愈性,但其应用仍存在争议。

涵盖领域

本文进行了一项综述,以研究目前支持在MM中使用allo-SCT的证据。我们研究了可能用于诱导骨髓瘤特异性免疫反应的新型细胞疗法,包括嵌合抗原受体(CAR)-T细胞和自然杀伤(NK)细胞这一充满前景的新领域。

专家观点

研究人员在探索allo方法时面临的主要争议之一是,最近观察到第二代和第三代蛋白酶体抑制剂、免疫调节药物、单克隆抗体和去乙酰化酶抑制剂在治疗方面有显著改善。尽管取得了这些巨大进展,但该疾病仍无法治愈,allo-SCT可能仍在MM的治愈中发挥作用。我们认为allo-SCT在MM中仍占有一席之地,应在对照临床试验中探索其在高危患者中的治愈潜力。诸如CAR技术等新型细胞疗法可能为潜在治愈开辟新的研究途径。目前正在进行的前瞻性研究的数据将有助于澄清悬而未决的临床问题。

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