CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell proliferation in vitro and in vivo.
CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell proliferation in vitro and in vivo.
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DOI：
10.1038/bcj.2014.15
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发表时间：
2014-03-21
影响因子：
12.8
通讯作者：
Liu, X. Y.
中科院分区：
文献类型：
--
作者：
Li, G.;Li, X.;Wu, H.;Yang, X.;Zhang, Y.;Chen, L.;Wu, X.;Cui, L.;Wu, L.;Luo, J.;Liu, X. Y.
我们在此报告了一种新策略，通过在病毒基因组中携带可溶性柯萨奇腺病毒受体（sCAR）-IL3表达盒形成Ad.IL3，将溶瘤腺病毒重定向至CD123，其通过CD123持续感染急性髓系白血病（AML）细胞。 Ad.IL3经过进一步改造，含有编码锰超氧化物歧化酶（MnSOD）或甘露糖结合植物凝集素半夏凝集素（PPA）的基因，形成Ad.IL3-MnSOD和Ad.IL3-PPA。与Ad.IL3或Ad.sp-E1A对照相比，Ad.IL3-MnSOD和Ad.IL3-PPA显着抑制HL60和KG-1细胞的体外增殖。在用 Ad.IL3-MnSOD 或 Ad.IL3-PPA 处理的 HL60 和 KG-1 细胞中检测到细胞凋亡升高。在 HL60 细胞中，caspase-9–caspase-7 途径被确定由 Ad.IL3-MnSOD 以及 Ad.IL3-PPA 激活。在 HL60/Luc 异种移植非肥胖糖尿病/严重联合免疫缺陷小鼠模型中，与 Ad.IL3 相比，Ad.IL3-MnSOD 和 Ad.IL3-PPA 抑制癌细胞生长。治疗后第 9 天，Ad.IL3 组和 Ad.IL3-PPA 组之间的癌细胞负荷存在显着差异。此外，与Ad.sp-E1A相比，Ad.IL3-MnSOD显着延长了小鼠的存活时间。这些发现表明 Ad.IL3 基因可以作为 AML 治疗的新型药物。在病毒基因组中携带 sCAR 配体表达盒可能提供一种通用方法，将溶瘤腺病毒重定向到抵抗血清型 5 腺病毒感染的癌细胞上的各种膜受体。
We report here a novel strategy to redirect oncolytic adenoviruses to CD123 by carry a soluble coxsackie-adenovirus receptor (sCAR)-IL3 expression cassette in the viral genome to form Ad.IL3, which sustainably infected acute myeloid leukemia (AML) cells through CD123. Ad.IL3 was further engineered to harbor gene encoding manganese superoxide dismutase (MnSOD) or mannose-binding plant lectin Pinellia pedatisecta agglutinin (PPA), forming Ad.IL3-MnSOD and Ad.IL3-PPA. As compared with Ad.IL3 or Ad.sp-E1A control, Ad.IL3-MnSOD and Ad.IL3-PPA significantly suppressed in vitro proliferation of HL60 and KG-1 cells. Elevated apoptosis was detected in HL60 and KG-1 cells treated with either Ad.IL3-MnSOD or Ad.IL3-PPA. The caspase-9–caspase-7 pathway was determined to be activated by Ad.IL3-MnSOD as well as by Ad.IL3-PPA in HL60 cells. In an HL60/Luc xenograft nonobese diabetic/severe-combined immunodeficiency mice model, Ad.IL3-MnSOD and Ad.IL3-PPA suppressed cancer cell growth as compared with Ad.IL3. A significant difference of cancer cell burden was detected between Ad.IL3 and Ad.IL3-PPA groups at day 9 after treatment. Furthermore, Ad.IL3-MnSOD significantly prolonged mouse survival as compared with Ad.sp-E1A. These findings demonstrated that Ad.IL3-gene could serve as a novel agent for AML therapy. Harboring sCAR-ligand expression cassette in the viral genome may provide a universal method to redirect oncolytic adenoviruses to various membrane receptors on cancer cells resisting serotype 5 adenovirus infection.
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影响因子：
5.2
作者：
Chen, Po-Ming;Wu, Tzu-Chin;Lee, Huei
通讯作者：
Lee, Huei
影响因子：
11.4
作者：
Black, JH;McCubrey, JA;Frankel, AE
通讯作者：
Frankel, AE
DOI：
10.1111/j.1365-2362.2007.01746.x
发表时间：
2007-01-01
影响因子：
5.5
作者：
Hauswirth, A. W.;Florian, S.;Valent, P.
通讯作者：
Valent, P.
影响因子：
4.4
作者：
Drake PM;Schilling B;Niles RK;Prakobphol A;Li B;Jung K;Cho W;Braten M;Inerowicz HD;Williams K;Albertolle M;Held JM;Iacovides D;Sorensen DJ;Griffith OL;Johansen E;Zawadzka AM;Cusack MP;Allen S;Gormley M;Hall SC;Witkowska HE;Gray JW;Regnier F;Gibson BW;Fisher SJ
通讯作者：
Fisher SJ
影响因子：
6.6
作者：
Duan, H;Zhang, HJ;Domann, FE
通讯作者：
Domann, FE