Interleukin-12: Murine models of a potent antitumor agent
Interleukin-12: Murine models of a potent antitumor agent
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DOI：
10.1111/j.1749-6632.1996.tb52676.x
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Palleroni, AV
中科院分区：
文献类型：
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作者：
Brunda, MJ;Luistro, L;Palleroni, AV
在克隆白细胞介素 12 (IL-12), 1, 2 后不久，人们对该细胞因子的潜在抗肿瘤作用产生了浓厚的兴趣。这种兴趣是基于其他细胞因子的效用，例如干扰素 α (IFN-a) 和白细胞介素 2 (IL-2) 作为肿瘤学适应症的治疗剂3 以及 IL-12.4-6 的生物学特性 IL-12 的特性包括诱导 T 细胞和自然杀伤 (NK) 细胞增殖、诱导细胞毒性淋巴细胞群（细胞毒性 T 细胞 [CTL]、NK 和淋巴因子激活的杀伤细胞） [LAK]细胞），刺激细胞因子分泌，特别是干扰素γ（IFN-I），以及诱导Th1辅助细胞亚群成熟的能力，其介导细胞介导的免疫反应。 IL-12 诱导这些作用的能力可能会导致对肿瘤生长的控制。由于人 IL-12 对鼠类细胞没有活性，因此人 IL-12 的潜在抗肿瘤特性只能在体外对人细胞进行测试，或者通过将人细胞转移到免疫缺陷动物体内进行有限的体内研究。除了能够刺激来自正常个体的细胞毒性T、NK和LAK细胞的体外活性之外，IL-1 2还增强了来自患有转移性实体瘤、I0毛细胞白血病、'* Sezary综合征'*或同种异体骨髓移植后的血液恶性肿瘤患者的免疫效应细胞的NK活性。同样，IL-12可以调节Sezary患者的PBMC产生的异常细胞因子。综合征 12；用 IL-12 培养这些患者的 PBMC 会增加刺激诱导的 IFN-的产生。）I 同时减少
Soon after the cloning of interleukin-12 (IL-12), 1, 2 a strong interest was generated in the potential antitumor effects of this cytokine. This interest was based on the utility of other cytokines, such as interferon alpha (IFN-a) and interleukin-2 (IL-2), as therapeutic agents for oncology indications3 and the biological properties of IL-12.4-6 Included among the properties of IL-12 are the induction of proliferation of T and natural killer (NK) cells, the induction of cytotoxic lymphoid populations (cytotoxic T cell [CTL], NK and lymphokine-activated killer [LAK] cells), the stimulation of cytokine secretion, especially interferon gamma (IFN-.) I), and the ability to induce maturation of the Thl helper cell subset, which mediates cellmediated immune responses. The ability of IL-12 to induce these effects may result in the control of tumor growth.Inasmuch as human IL-12 is inactive on murine cells,'the potential antitumor properties of human IL-12 can only be tested on human cells in vitro or in limited in vivo studies by transfer with human cells into immunodeficient animals. In addition to its abilities to stimulate in vitro activity of cytotoxic T, NK, and LAK cells from normal individual^,^^^ IL-I 2 augmented NK activity of immune effector cells from patients with metastatic solid tumors, I0 hairy cell leukemia,'* Sezary syndrome,'* or with hematologic malignancies after allogeneic bone marrow transplant." Likewise, IL-12 can modulate aberrant cytokine production by PBMC from patients with Sezary syndrome12; incubation of PBMC from these patients with IL-12 increased their stimulus-induced production of IFN-.) I while decreasing