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通过纳米脂体 epacadostat 和 docetaxel 组合进行化学免疫疗法,以抑制 IDO1 和抑制瘤微环境

Rahimeh Khoshkhabar¹, Mona Yazdani², Seyedeh Hoda Alavizadeh¹

¹Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

International immunopharmacology

|June 13, 2024

概括

将IDO1抑制剂脂质体 epacadostat (Lip-EPA) 与多塞 (DTX) 化疗结合起来可以增强抗瘤免疫力. 这种组合有效地减少了瘤生长,并通过调节瘤微环境来改善存活率.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
药理学药理学是指药理学的学科.

背景情况:

过度激活的托代谢通过胺二二氧化酶-1 (IDO1) 促进瘤免疫逃脱和治疗失败.
埃帕卡多斯塔特 (EPA) 是一种有效的IDO1抑制剂,但单一治疗显示出不足的抗瘤活性.
多塞塔克塞尔 (DTX) 作为一种补充免疫细胞死亡 (ICD) 剂.

研究的目的:

评估与B16F10黑色素瘤模型相比,用脂质体 epacadostat (Lip-EPA) 和 docetaxel (DTX) 同时治疗的疗效.
评估这种联合治疗对瘤微环境和免疫反应的影响.

主要方法:

在体外评估epacadostat (EPA) 和docetaxel (DTX) 的组合指数 (CI).
在B16F10模型中的体内疗效研究.
免疫分析,组织病理学分析,以及瘤生长延迟 (TGD) 和延长寿命 (ILS) 的评估.

主要成果:

在用组合治疗的B16F10细胞中观察到协同作用的细胞毒性作用.
在T淋巴细胞和IFN-γ显著增加,调节性T细胞 (Treg) 和IL-10水平下降.
显著的瘤生长延迟 (69.15%) 和增加寿命 (>47.83%) 与Lip-EPA + DTX治疗.
在瘤组合治疗后增加的三 (Trp) 和降低的 kynurenine (Kyn) 水平.

结论:

脂质体 epacadostat 与多塞塔克塞尔化疗相结合显著增强抗瘤免疫反应.
这种组合有效地克服了瘤的免疫抑制微环境.
IDO1抑制剂的纳米脂质体配方需要在联合癌症治疗中进一步研究.

关键词:

化疗-免疫疗法是一种化学免疫疗法.这是多西塔克塞尔.这是一种IDO1抑制剂.黑色素瘤是一种黑色素瘤.瘤微环境是一个微环境.

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