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J Clin Invest：化疗耐受的急性淋巴细胞性白血病治疗新希望

2015-01-29 佚名 生物谷

急性淋巴细胞白血病
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急性淋巴细胞性白血病（ALL）是儿童白血病最常见的形式。治疗方案主要以化疗为主。可对化疗药物的耐受却是当今ALL治疗一直难以克服的一个障碍。美国洛杉矶儿童医院的科研究员最近设计并开发了一种以新型蛋白质为基础的治疗，被证实对耐药的白血病细胞非常有效。这篇研究近日在线发表在Journal of Clinical Investigation。 15岁以下儿童癌症患者有25%都是ALL患者。历史上A

急性淋巴细胞性白血病（ALL）是儿童白血病最常见的形式。治疗方案主要以化疗为主。可对化疗药物的耐受却是当今ALL治疗一直难以克服的一个障碍。美国洛杉矶儿童医院的科研究员最近设计并开发了一种以新型蛋白质为基础的治疗，被证实对耐药的白血病细胞非常有效。这篇研究近日在线发表在Journal of Clinical Investigation。

15岁以下儿童癌症患者有25%都是ALL患者。历史上ALL有较高的死亡率，曾80%的患者都无法幸存。不过如今，这些数字已发生逆转，几乎80%的ALL儿童都能实现长期生存。不过仍有20%的孩子在与白血病做生死较量。研究人员的目的就是为了帮助这些20%的耐受化疗药物的ALL儿童。

肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis-inducing ligand，TRAIL）由免疫细胞产生，通过结合两个所谓的"死亡受体"-TRAILR1和TRAILR2，诱导细胞凋亡。研究人员认为TRAIL是人体免疫系统产生的一种能杀死肿瘤细胞却对正常细胞无任何毒性的天然成分。但是之前使用TRAIL作为抗癌药物的临床试验却并不是很成功，主要原因是除了肿瘤细胞，还有其他细胞也能产生类似受体。

于是研究人员确定了一种以前未知的蛋白质-CD19，特殊之处是CD19几乎在所有ALL细胞中都有表达。利用这一点，他们通过基因工程技术将CD19的配体基因和TRAIL基因融合，产生的融合蛋白被命名为-"CD19L-sTRAIL"，这样CD19配体直接帮助TRAIL特异性的诱导含有CD19的ALL细胞凋亡。实验证明，CD19L-sTRAIL定位到ALL细胞的能力比单独TRAIL强100,000倍，而且CD19L-sTRAIL能杀死99%的ALL细胞-无论在培养皿上或者是小鼠实验上。两到三个剂量的CD19L-sTRAIL注射也显著改善了被引入致死剂量的人ALL细胞的小鼠的存活率，并且未观察到有副作用。研究人员还表明CD19L-sTRAIL在小鼠身上的疗效比标准组合药物化疗或者放射治疗都更明显。

CD19L-sTRAIL的研发，将会为儿童ALL复发后治疗提供另外一个有效方案。

原始出处

Uckun FM, Myers DE, Qazi S, Ozer Z, Rose R, D'Cruz OJ, Ma H.Recombinant human CD19L-sTRAIL effectively targets B cell precursor acute lymphoblastic leukemia.J Clin Invest. 2015 Jan 26

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    2015-06-21 xiangyuzhou971

    #EST#

    0

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    2015-07-29 珙桐

    #新希望#

    0

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    2015-04-03 lqrandywkz

    #细胞性#

    0

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    2015-02-17 chinayinhan

    已阅

    0

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    2015-01-31 wetgdt

    #淋巴细胞#

    0

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    2015-01-29 223.104.5.**

    有针对CD19抗体

    0

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