IL-24: A novel gene therapy candidate for immune system upregulation in Hodgkin’s lymphoma

Maryam Erfan Manesh , Abdolreza Esmaeilzadeh , Mehri Hajikhan Mirzaei
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引用次数: 21

Abstract

Hodgkin’s Lymphoma (HL) as a prevalent hematolymphoid malignancy begins in cells of immune system and is characterized by the specific histologic, clinical properties. Abnormality in apoptosis has been recognized as a crucial pathway in its progression. Nowadays, 35–40% of patients in stages III and IV show disease relapse or symptoms of refractory to first-line chemotherapy; therefore, novel treatment strategies are required. As apoptosis inducing is an important mechanism in cancer treatments, novel anticancer molecules to induce programmed cell death are required. The authors present a novel therapeutic approach for HL, with regard to anti-tumoral and immunomodulatory effects of the mda-7/IL-24. This gene, located in human chromosome 1q32-33, has shown tumor suppressor activity in various human malignant cells in, in vitro, in vivo, and even in clinical trial studies. Our hypothesis was designed to evaluate anti- tumoral effects of mda-7/IL-24 in SCID mice model using the adenovirus-based vector. mda-7/IL-24 interestingly has antiangiogenic, immunomodulatory, and bystander antitumoral activities. mda-7/IL-24 can suppress anti-apoptotic Bcl-2 family proteins, and induces GADD family, Bak, Bax, and other pro-apoptosis proteins. This hypothesis suggests that adenovirus vectors expressing mda-7/IL-24 may help for effective immunotherapies of HL.

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IL-24:霍奇金淋巴瘤免疫系统上调的新基因治疗候选物
霍奇金淋巴瘤(Hodgkin’s Lymphoma, HL)是一种起源于免疫系统细胞的普遍的血淋巴恶性肿瘤,具有特殊的组织学、临床特征。细胞凋亡异常已被认为是其发展的重要途径。目前,35-40%的III期和IV期患者出现疾病复发或一线化疗难治性症状;因此,需要新的治疗策略。细胞凋亡诱导是肿瘤治疗的重要机制,需要新的抗肿瘤分子来诱导程序性细胞死亡。作者提出了一种新的治疗HL的方法,关于mda-7/IL-24的抗肿瘤和免疫调节作用。该基因位于人类染色体1q32-33中,在体外、体内甚至临床试验研究中,对各种人类恶性细胞都显示出抑瘤活性。我们的假设是利用腺病毒载体评价mda-7/IL-24在SCID小鼠模型中的抗肿瘤作用。有趣的是,mda-7/IL-24具有抗血管生成、免疫调节和旁观者抗肿瘤活性。mda-7/IL-24可抑制抗凋亡Bcl-2家族蛋白,诱导GADD家族、Bak、Bax等促凋亡蛋白。这一假设提示表达mda-7/IL-24的腺病毒载体可能有助于HL的有效免疫治疗。
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