• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>EBioMedicine >Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice
【2h】

Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice

机译：低剂量全身照射结合重组CD19-配体×可溶性TRAIL融合蛋白对小鼠抗辐射的B前体急性淋巴母细胞白血病高度有效

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In high-risk remission B-precursor acute lymphoblastic leukemia (BPL) patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT) even after the use of very intensive total body irradiation (TBI)-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD) burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL”) fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI) combined with CD19L–sTRAIL was highly effective against (1) xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS) mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2) radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT.
机译：在高风险缓解的B前体急性淋巴细胞白血病（BPL）患者中，即使在使用非常密集的全身照射（TBI）为基础的调节方案后，造血干细胞移植（HSCT）后的复发率仍然很高，尤其是在高“最小残留疾病”（MRD）负担的患者。因此，迫切需要能够杀死抗辐射的BPL细胞并选择性增强其辐射敏感性的新试剂。我们报告了临床前原理证明，通过将放射线与重组人CD19-配体×可溶性TRAIL（“ CD19L–sTRAIL”）融合蛋白相结合，可以增强针对BPL的放射疗法的效力。 CD19L-sTRAIL持续杀死来自BPL患者的抗辐射原发性白血病细胞以及BPL异种移植细胞及其引发白血病的体内克隆性成分。低剂量全身照射（TBI）与CD19L–sTRAIL结合对NOD / SCID（NS）小鼠体内的（1）异种移植的抗CD19 + 放射化学治疗的人BPL具有很高的抵抗力，而NOD / SCID（NS）小鼠则受到同样致命的剂量CD22ΔE12xBCR-ABL双转基因小鼠中，来自复发性BPL患者的异种移植细胞以及（2）具有淋巴瘤特征的抗辐射晚期CD19 + 鼠BPL。我们假设将CD19L-sTRAIL纳入高危BPL患者的移植前TBI方案将改善HSCT后的生存结局。

著录项

相似文献

  • 外文文献
  • 中文文献
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号