Penn State College of Medicine, Hershey, PA, USA.
Cancer Biol Ther. 2010 Sep 15;10(6):625-31. doi: 10.4161/cbt.10.6.12653. Epub 2010 Sep 13.
Cationic lipid DNA complex (CLDC) is an immunostimulatory preparation that has significant anti-leukemic effects in multiple murine models of leukemia: BCR-ABL(+) myelogenous leukemia in C3H/HeJ animals and myelomonocytic leukemia in BALB/c mice. Following leukemic challenge, CLDC treatment inhibits tumor cell growth in vivo and extends survival, sometimes resulting in apparent eradication of tumor cells. CLDC induces multiple cytokines including interferon-gamma (IFNγ), and intravenous treatment results in a more rapid and robust response than subcutaneous treatment. IFNγ is induced in a dose-dependent manner, and tachyphylaxis results from repeated doses of CLDC. Tachyphylaxis of therapeutic effects is exacerbated at higher doses, thus the optimal survival benefits are seen at intermediate doses. Animals whose leukemia has been successfully treated with CLDC exhibit a survival advantage when faced with a secondary leukemic challenge, suggesting the existence of an adaptive anti-leukemic response. This work demonstrates the effectiveness of CLDC in multiple experimental leukemias and is consistent with a stimulation of a lasting TH(1) anti-leukemic immune response.
阳离子脂质体 DNA 复合物(CLDC)是一种免疫刺激性制剂,在多种白血病的小鼠模型中具有显著的抗白血病作用:C3H/HeJ 动物中的 BCR-ABL(+)髓性白血病和 BALB/c 小鼠中的骨髓单核细胞白血病。在白血病挑战后,CLDC 治疗可抑制体内肿瘤细胞的生长并延长存活期,有时可导致肿瘤细胞明显消除。CLDC 诱导多种细胞因子,包括干扰素-γ(IFNγ),静脉内治疗比皮下治疗产生更快、更强的反应。IFNγ呈剂量依赖性诱导,CLDC 的重复剂量会导致快速耐受。在更高剂量下,治疗效果的快速耐受会加剧,因此在中等剂量下可获得最佳的生存获益。成功用 CLDC 治疗白血病的动物在面临二次白血病挑战时表现出生存优势,这表明存在适应性抗白血病反应。这项工作证明了 CLDC 在多种实验性白血病中的有效性,并且与持续的 TH(1)抗白血病免疫反应的刺激一致。