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使用树突状细胞治疗多发性骨髓瘤的免疫疗法:如何改进?

Immunotherapy using dendritic cells against multiple myeloma: how to improve?

作者信息

Nguyen-Pham Thanh-Nhan, Lee Yoon-Kyung, Kim Hyeoung-Joon, Lee Je-Jung

机构信息

Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, Republic of Korea.

出版信息

Clin Dev Immunol. 2012;2012:397648. doi: 10.1155/2012/397648. Epub 2012 Mar 15.

Abstract

Multiple myeloma (MM) is a good target disease in which one can apply cellular immunotherapy, which is based on the graft-versus-myeloma effect. This role of immune effector cells provides the framework for the development of immune-based therapeutic options that use antigen-presenting cells (APCs) with increased potency, such as dendritic cells (DCs), in MM. Current isolated idiotype (Id), myeloma cell lysates, myeloma dying cells, DC-myeloma hybrids, or DC transfected with tumor-derived RNA has been used for immunotherapy with DCs. Immunological inhibitory cytokines, such as TGF-β, IL-10, IL-6 and VEGF, which are produced from myeloma cells, can modulate antitumor host immune response, including the abrogation of DC function, by constitutive activation of STAT3. Therefore, even the immune responses have been observed in clinical trials, the clinical response was rarely improved following DC vaccinations in MM patients. We are going to discuss how to improve the efficacy of DC vaccination in MM.

摘要

多发性骨髓瘤(MM)是一种适合应用细胞免疫疗法的理想靶疾病,该疗法基于移植物抗骨髓瘤效应。免疫效应细胞的这一作用为开发基于免疫的治疗方案提供了框架,这些方案在MM中使用具有更强效力的抗原呈递细胞(APC),如树突状细胞(DC)。目前,分离的独特型(Id)、骨髓瘤细胞裂解物、骨髓瘤死亡细胞、DC-骨髓瘤杂交细胞或用肿瘤衍生RNA转染的DC已用于DC免疫治疗。骨髓瘤细胞产生的免疫抑制细胞因子,如转化生长因子-β(TGF-β)、白细胞介素-10(IL-10)、白细胞介素-6(IL-6)和血管内皮生长因子(VEGF),可通过信号转导和转录激活因子3(STAT3)的组成性激活来调节抗肿瘤宿主免疫反应,包括废除DC功能。因此,尽管在临床试验中观察到了免疫反应,但MM患者接受DC疫苗接种后临床反应很少得到改善。我们将讨论如何提高MM中DC疫苗接种的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/403f/3312256/e1afc2cf2f5a/CDI2012-397648.001.jpg

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