J Immunother Cancer:纳米胶囊化的利妥昔单抗在具有补体活性的人源化小鼠模型中介导对转移性B细胞淋巴瘤的优异细胞免疫

2021-03-08 MedSci原创 MedSci原创

治疗性单克隆抗体(mAbs),如抗CD20利妥昔单抗(RTX)治疗非霍奇金淋巴瘤(NHL)和曲妥珠单抗/赫赛汀治疗乳腺癌(抗Her2)改变了传统的癌症治疗方式,使癌症治疗发生了革命性的变化。

治疗性单克隆抗体(mAbs),如抗CD20利妥昔单抗(RTX)治疗非霍奇金淋巴瘤(NHL)和曲妥珠单抗/赫赛汀治疗乳腺癌(抗Her2)改变了传统的癌症治疗方式,使癌症治疗发生了革命性的变化。然而,许多先前开发的用于癌症研究的小鼠模型由于其缺乏或非人类免疫系统,在评估基于免疫系统的癌症治疗方面的效用有限。

为了创造一个成功植入人类细胞的优越系统,缺乏共同细胞因子受体γ链(IL- 2Rγ)的高级免疫缺陷NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ(NSG)小鼠被开发并广泛使用。NSG小鼠的免疫系统严重受损,主要包括B细胞、T细胞和自然杀伤细胞的发育、树突细胞功能和巨噬细胞活性降低以及先天性免疫缺陷。

虽然NSG小鼠被认为对肿瘤异种移植有效,但单克隆抗体的治疗作用主要是通过抗体诱导的细胞凋亡来实现的。因此,由于缺乏对其他抗体介导的细胞毒性机制的支持,如补体依赖性细胞毒性(CDC)、抗体依赖性细胞毒性(ADCC)或抗体依赖性细胞吞噬作用(ADCP),NSG株不能用于完整评估mAbs活性。

本研究利用一种新的NSG菌株建立了一种人源化小鼠模型,即NOD.Cg-Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG-Hc1)。除了人源化赋予的其他机制外,它还包含支持CDC的Hc基因的校正突变。通过利用这个模型,本研究重新评估了纳米胶囊化的利妥昔单抗在人Burkitt淋巴瘤细胞系2F7-BR44异种移植后的抗癌效果。

研究结果正如预期的那样,与亲代NSG株相比,异种移植的人源化NSG-Hc1小鼠,其支持天然利妥昔单抗具有更好的淋巴瘤清除。纳米胶囊化的利妥昔单抗与CXCL13结合作为淋巴瘤的靶向配体,进一步增强了NSG-Hc1小鼠的抗淋巴细胞瘤活性,更重要的是,其介导了抗淋巴细胞瘤细胞反应。

综上所述,NSG-Hc1小鼠可以作为一个可行的模型,既可以用于研究使用癌症靶向的抗肿瘤治疗,也可以了解抗肿瘤细胞免疫反应的诱导机制。

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    2021-03-10 科研科研科研

    细胞免疫激活

    0

  5. 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    2021-02-25 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0

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