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急性白血病中的免疫疗法:使用WT1抗原的意义与前景

Immunotherapy in Acute Leukemias: Implications and Perspectives Using Wt1 Antigen.

作者信息

Cebinelli Guilherme Cesar Martelossi, DE Sousa Pereira Nathália, Sena Michelle Mota, DE Oliveira Carlos Eduardo Coral, Fujita Thiago Cezar, DA Rocha Sérgio Paulo Dejato, DE Abreu Oliveira Francisco José, Marinello Poliana Camila, Watanabe Maria Angelica Ehara

机构信息

Laboratory of Molecular Genetics and Immunology, Biological Sciences Center, State University of Londrina, Londrina-Paraná, Brazil.

Laboratory of Studies and Application of DNA Polymorphisms, Biological Sciences Center, State University of Londrina, Londrina-Paraná, Brazil.

出版信息

Anticancer Res. 2016 Aug;36(8):3795-802.

Abstract

The WT1 gene encodes a transcription factor involved in regulation of many cellular processes, including proliferation, differentiation, mRNA processing and apoptosis, besides acting as a transcription repressor of growth factors and their receptors' genes. This gene is expressed at high levels in several types of cancers, including acute leukemias. In this regard, many studies have identified WT1 protein as a tumor antigen, considered a target molecule for clinical application in human acute leukemias. Immunotherapy using WT1 antigen has been effective in stimulating immune responses against leukemic cells. Regarding adoptive immunotherapy, the use of dendritic cells (DCs) for the WT1-specific cytotoxic T cells generation proved to be efficient in the development and maintenance of immunologic cells. Therefore, these therapeutic methods, that provided enthusiasm for moving ahead, highlight several opportunities and challenges to be used in clinical practice for managing acute leukemias.

摘要

WT1基因编码一种转录因子,除了作为生长因子及其受体基因的转录抑制因子外,还参与调控许多细胞过程,包括增殖、分化、mRNA加工和细胞凋亡。该基因在包括急性白血病在内的多种癌症中高水平表达。在这方面,许多研究已将WT1蛋白鉴定为肿瘤抗原,被认为是人类急性白血病临床应用的靶分子。使用WT1抗原的免疫疗法在刺激针对白血病细胞的免疫反应方面已取得成效。关于过继性免疫疗法,事实证明,利用树突状细胞(DC)生成WT1特异性细胞毒性T细胞在免疫细胞的发育和维持方面是有效的。因此,这些为向前发展带来希望的治疗方法凸显了在临床实践中用于治疗急性白血病的若干机遇和挑战。

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