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首页> 外文期刊>Journal of Molecular Biochemistry >Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model
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Therapeutic efficacy of an oncolytic adenovirus containing RGD ligand in minor capsid protein IX and Fiber, Δ24DoubleRGD, in an ovarian cancer model

机译：含RGD配体的溶瘤腺病毒对次要衣壳蛋白IX和纤维Δ24DoubleRGD的治疗功效在卵巢癌模型中

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Ovarian cancer is the leading cause of gynecological disease death despite advances in medicine. Therefore, novel strategies are required for ovarian cancer therapy. Conditionally replicative adenoviruses (CRAds), genetically modified as anti-cancer therapeutics, are one of the most attractive candidate agents for cancer therapy. However, a paucity of coxsackie B virus and adenovirus receptor (CAR) expression on the surface of ovarian cancer cells has impeded treatment of ovarian cancer using this approach.This study sought to engineer a CRAd with enhanced oncolytic ability in ovarian cancer cells, “Δ24DoubleRGD.” Δ24DoubleRGD carries an arginine-glycine-aspartate (RGD) motif incorporated into both fiber and capsid protein IX (pIX) and its oncolytic efficacy was evaluated in ovarian cancer. In vitro analysis of cell viability showed that infection of ovarian cancer cells with Δ24DoubleRGD leads to increased cell killing relative to the control CRAds. Data from this study suggested that not only an increase in number of RGD motifs on the CRAd capsid, but also a change in the repertoir of targeted integrins could lead to enhanced oncolytic potency of Δ24DoubleRGD in ovarian cancer cells in vitro. In an intraperitoneal model of ovarian cancer, mice injected with Δ24DoubleRGD showed, however, a similar survival rate as mice treated with control CRAds.
机译：尽管医学进步，卵巢癌仍是导致妇科疾病死亡的主要原因。因此，卵巢癌治疗需要新的策略。基因修饰为抗癌治疗剂的条件复制腺病毒（CRAd）是最有吸引力的癌症治疗候选药物之一。然而，这种方法在卵巢癌细胞表面缺乏少量的柯萨奇B病毒和腺病毒受体（CAR）表达阻碍了卵巢癌的治疗。本研究旨在设计出具有增强的溶瘤能力的CRAd卵巢癌细胞，“Δ24DoubleRGD” 。” Δ24DoubleRGD带有掺入纤维和衣壳蛋白IX（pIX）的精氨酸-甘氨酸-天冬氨酸（RGD）基序，并在卵巢癌中评估了其溶瘤功效。细胞活力的体外分析表明，相对于对照CRAd，用Δ24DoubleRGD感染卵巢癌细胞会导致杀伤力增加。这项研究的数据表明，不仅CRAd衣壳上的RGD基序数量增加，而且靶向整联蛋白库的变化也可能导致体外卵巢癌细胞中Δ24DoubleRGD的溶瘤作用增强。然而，在卵巢癌的腹膜内模型中，注射Δ24DoubleRGD的小鼠的存活率与对照CRAds的小鼠相似。

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