Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.
Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.
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DOI：
10.1038/bjc.1994.52
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发表时间：
1994-02
影响因子：
8.8
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中科院分区：
文献类型：
--
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将人类 T 细胞急性淋巴细胞白血病 (T-ALL) 细胞系 HSB-2 移植到严重联合免疫缺陷 (SCID) 小鼠体内，发现会产生与人类相似的播散性白血病模式。静脉注射 10(7) HSB-2 细胞与普遍致命的白血病有关。对动物的组织病理学检查显示，白血病最初从骨髓扩散到包括脑膜在内的所有主要器官。通过将抗 CD7 MAb HB2 与核糖体失活蛋白皂草素缀合构建了免疫毒素 (HB2-Sap)。体外蛋白质合成抑制测定显示 HB2-Sap 免疫毒素 (IT) 特异性递送至 CD7+ HSB-2 靶细胞，IC50 为 4.5 pM。当给 SCID 小鼠注射 10(6) 个 HSB-2 细胞，然后在 8 天后用单次静脉内剂量的 10 微克免疫毒素进行治疗时，与未治疗的对照组相比，治疗组中存活的动物数量证明了显着的治疗效果（χ 2 = 5.348，P = 0.021）。这些结果证明了人类白血病异种移植物在 SCID 小鼠中的有用应用以及抗 CD7 免疫毒素在人类 T-ALL 中的潜在治疗效果。
The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to produce a disseminated pattern of leukaemia similar to that seen in man. The intravenous injection of 10(7) HSB-2 cells was associated with a universally fatal leukaemia. Histopathological examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving in the therapy group compared with untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the useful application of human leukaemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 immunotoxin in human T-ALL.