Adenovirus as a new agent for multiple myeloma therapies: Opportunities and restrictions.

The Korean Journal of Hematology Pub Date : 2011-12-01 Epub Date: 2011-12-27 DOI:10.5045/kjh.2011.46.4.229
Svjetlana Raus, Silvia Coin, Vladia Monsurrò
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引用次数: 12

Abstract

Multiple myeloma is a malignancy of B-cells that is characterized by the clonal expansion and accumulation of malignant plasma cells in the bone marrow. This disease remains incurable, and a median survival of 3-5 years has been reported with the use of current treatments. Viral-based therapies offer promising alternatives or possible integration with current therapeutic regimens. Among several gene therapy vectors and oncolytic agents, adenovirus has emerged as a promising agent, and it is already being used for the treatment of solid tumors in humans. The main concern with the clinical use of this vector has been its high immunogenicity; adenovirus is often able to induce a strong immune response in the host. Furthermore, new limitations in the efficacy of this therapy, intrinsic to the nature of tumor cells, have been recently observed. For example, our group showed a strong antiviral phenotype in vitro and in vivo in a subset of tumors, shedding new insights that may explain the partial failure of clinical trials based on this promising new therapy. In this review, we describe novel therapeutic approaches that implement viral-based treatments in hematological malignancies and address the novelty as well as the possible limitations of these new therapies, especially in the context of the use of adenoviral vectors for treating multiple myeloma.

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腺病毒作为多发性骨髓瘤治疗的新药物:机遇与限制。
多发性骨髓瘤是一种b细胞恶性肿瘤,其特征是骨髓中恶性浆细胞的克隆性扩增和积累。这种疾病仍然无法治愈,据报道,使用目前的治疗方法,中位生存期为3-5年。基于病毒的疗法提供了有希望的替代方案或与当前治疗方案的可能整合。在多种基因治疗载体和溶瘤剂中,腺病毒已成为一种很有前途的药物,并已被用于人类实体瘤的治疗。该载体临床应用的主要问题是其高免疫原性;腺病毒通常能在宿主体内引起强烈的免疫反应。此外,最近观察到这种疗法的疗效有新的局限性,这是肿瘤细胞固有的性质。例如,我们的研究小组在体外和体内的肿瘤亚群中显示出强烈的抗病毒表型,这可能解释了基于这种有希望的新疗法的临床试验的部分失败。在这篇综述中,我们描述了在血液系统恶性肿瘤中实施基于病毒的治疗的新治疗方法,并讨论了这些新疗法的新颖性以及可能的局限性,特别是在使用腺病毒载体治疗多发性骨髓瘤的背景下。
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