Raus Svjetlana, Coin Silvia, Monsurrò Vladia
Department of Pathology and Diagnostics, University of Verona Medical School, Verona, Italy.
Korean J Hematol. 2011 Dec;46(4):229-38. doi: 10.5045/kjh.2011.46.4.229. Epub 2011 Dec 27.
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.
多发性骨髓瘤是一种B细胞恶性肿瘤,其特征是恶性浆细胞在骨髓中克隆性扩增和聚集。这种疾病仍然无法治愈,据报道,使用当前治疗方法的中位生存期为3至5年。基于病毒的疗法提供了有前景的替代方案或可能与当前治疗方案相结合。在几种基因治疗载体和溶瘤剂中,腺病毒已成为一种有前景的药物,并且已经用于人类实体瘤的治疗。该载体临床应用的主要问题一直是其高免疫原性;腺病毒通常能够在宿主中诱导强烈的免疫反应。此外,最近观察到这种疗法的疗效存在新的局限性,这是肿瘤细胞性质所固有的。例如,我们的研究小组在一部分肿瘤中在体外和体内均显示出强烈的抗病毒表型,这为解释基于这种有前景的新疗法的临床试验部分失败提供了新的见解。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治疗的新型治疗方法,并探讨了这些新疗法的新颖性以及可能的局限性,尤其是在使用腺病毒载体治疗多发性骨髓瘤的背景下。