Reversal of acute myelogenous leukemia in humanized SCID mice using a novel adoptive transfer approach.
Reversal of acute myelogenous leukemia in humanized SCID mice using a novel adoptive transfer approach.
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使用新型过继转移方法逆转人源化 SCID 小鼠的急性髓性白血病。
DOI：
10.1172/jci117422
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Santoli,D
中科院分区：
文献类型：
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作者：
Cesano,A;Visonneau,S;Cioe,L;Clark,SC;Rovera,G;Santoli,D
晚期人类恶性肿瘤不能通过过继转移自体淋巴因子激活的杀伤(LAK)细胞来永久治愈。此外，在体内应用高剂量的IL-2来维持LAK的活性与严重的毒性有关。在这项研究中，我们测试了一种唯一有效的MHC非限制性人类杀伤T细胞克隆(TALL-104)在人源化严重联合免疫缺陷(SCID)急性髓系白血病(AML)小鼠中的抗肿瘤效果。我们发现，在适当的实验条件下，TALL-104细胞可以有效地逆转粒-单核细胞白血病细胞系U937在SCID小鼠组织中的侵袭性生长，导致AML的完全消除。在肿瘤攻击时将TALL-104细胞与重组人(Rh)IL-12(1微克/天)联合单次转移可显著延长小鼠的寿命。然而，根据临床和聚合酶链式反应的监测，白血病的根除是通过近距离重复注射效应器实现的。经致死性照射(非增殖期)的TALL-104细胞与低剂量的rh IL-2(100U/d)联合移植也可获得完全治愈。最值得注意的是，在疾病晚期接受多次转移无细胞因子的TALL-104细胞的小鼠中，50%的小鼠临床治愈，50%的小鼠存活时间显著延长。讨论了TALL-104细胞作为一种有效和安全的白血病净化剂的潜力。
Advanced human malignancies cannot be permanently cured by adoptive transfer of autologous lymphokine-activated killer (LAK) cells. Moreover, administration of high doses of IL-2 to maintain LAK activity in vivo is associated with severe toxicity. In this study, we tested the anti-tumor efficacy of a uniquely potent MHC non-restricted human killer T cell clone (TALL-104) in humanized severe combined immunodeficient (SCID) mice bearing acute myelogenous leukemia (AML). We show that, in appropriate experimental conditions, TALL-104 cells could effectively reverse the aggressive growth of the myelomonocytic leukemia cell line U937 in SCID mouse tissues, leading to complete abrogation of AML. A single transfer of TALL-104 cells at the time of tumor challenge in combination with recombinant human (rh) IL-12 (1 microgram/d) prolonged significantly the life of the mice. However, eradication of leukemia, as monitored both clinically and by PCR, was achieved by repeated injection of the effectors at close intervals. Complete cure was obtained also upon transfer of lethally irradiated (non-proliferating) TALL-104 cells together with low doses of rh IL-2 (100 U/d). Most notably, of the mice that received multiple transfers of TALL-104 cells without cytokines in an advanced disease stage, 50% were clinically cured, and 50% survived significantly longer. The potential of TALL-104 cells as an effective and safe leukemia purging agent is discussed.Images