BMJ子刊：重磅！研究证实抗肿瘤新药物——VCN-01可破坏胰腺癌间质并发挥抗肿瘤作用！

2021-11-14 MedSci原创 MedSci原创

VCN-01是一种具有直接抗肿瘤作用和间质破坏能力的溶瘤腺病毒，可作为治疗间质致密肿瘤的新药物。

胰腺导管腺癌(PDAC)是最致命的肿瘤之一，迄今为止取得的研究进展微乎其微，胰腺癌的5年的总生存率仍然是10%，并且在过去30年里没有明显的改善。PDAC的特征之一是一种密集的间质，它穿透并包围肿瘤，远远超过其他肿瘤类型。VCN-01是一种溶瘤腺病毒，能够在功能失调的RB1途径的癌细胞中复制并表达透明质酸酶，那么这种病毒对肿瘤有没有作用呢？有研究者评估了VCN-01在临床前模型和胰腺癌患者中的作用机制。

在免疫缺陷和免疫活性强的临床前模型中，通过静脉或瘤内给药，单独或联合标准化疗评估VCN-01的复制和抗肿瘤疗效。透明质酸酶活性通过组织化学染色和测量药物在肿瘤中的传递来评估。在一项概念验证临床试验中，VCN-01在联合化疗的情况下，以高达 1×10¹¹ 病毒颗粒的剂量给PDAC患者进行肿瘤内注射。ELISA法检测血清透明质酸酶表达，内镜超声弹性成像法检测肿瘤内透明质酸酶活性。

试验结果表明VCN-01可在PDAC模型中复制，并具有抗肿瘤作用，联合化疗后抗肿瘤作用增强。VCN-01表达的透明质酸酶可降解肿瘤间质，促进多种治疗药物的递送，如化疗和治疗性抗体。

VCN-01使肿瘤对化疗敏感，从而增强抗肿瘤活性

在患者血液中检测到VCN-01，显示治疗后20-28天的病毒复制高峰

临床上，治疗耐受性良好，导致注射病灶的病情稳定。VCN-01在血液和治疗后的肿瘤活检中可被检测到，表明病毒复制。随着时间的推移，患者血清中透明质酸酶水平升高，肿瘤硬度降低，提示间质破坏。

透明质酸酶PH20的表达和VCN-01对患者间质的破坏作用

总之，本研究表明VCN-01是一种具有直接抗肿瘤作用和间质破坏能力的溶瘤腺病毒，可作为治疗间质致密肿瘤的新药物。

参考文献：Bazan-Peregrino M, Garcia-Carbonero R, Laquente B, et al. VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects. Journal for ImmunoTherapy of Cancer 2021;9:e003254. doi: 10.1136/jitc-2021-003254

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2022-07-04 yykkxiaodou

#抗肿瘤新药#

57 0
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2022-01-27 ms1065684921169360

#新药物#

51 0
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2022-05-25 july_975

#肿瘤新药#

36 0
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2022-07-18 gaoxiaoe

#BMJ#

38 0
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2022-04-22 丁鹏鹏

#并发#

35 0
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2021-11-21 hykd12345

胰腺癌的间质靶标仍然是热点

65 0
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2021-11-16 xxxx1054

#重磅#

36 0
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2021-11-14 JZ Yang

感谢分享

74 0
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2021-11-14 徐Mia

厉害了

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BMJ子刊：重磅！研究证实抗肿瘤新药物——VCN-01可破坏胰腺癌间质并发挥抗肿瘤作用！

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