Mechanisms of Antitumor Action of Human Interferon

我们现在已经证明，干扰素α和伽玛单核细胞共培养在体外和体内都能够杀死卵巢肿瘤细胞，并且这两种干扰素的存在是杀瘤作用所必需的。此外，我们已经证明，单核细胞与α和伽马干扰素结合标准化疗药物紫杉醇和卡铂可以增加对靶肿瘤细胞的杀伤率。我们已经证明，10个卵巢癌细胞株对这种治疗方案敏感。此外，我们扩大了这一观察范围，以表明从健康捐赠者的全血中分离出来的单核细胞能够在体外杀死细胞。我们还对干扰素处理的单核细胞进行了先进的微阵列分析，以确定哪些蛋白质(S)在体内介导细胞死亡。该阵列已经确定了一些目标基因，以供验证和进一步研究。我们一直在与Annunziata博士合作分离卵巢癌患者的单核细胞。我们发现，与年龄匹配的健康人对照组相比，患者单核细胞是卵巢癌细胞系的有效杀手。

We have now shown that co-culture of Interferon alpha and gamma primed monocytes are capable of killing ovarian tumor cells both in vitro and in vivo, and the presence of both interferons is necessary for the tumorcidal effect. Further, we have shown that monocytes primed with alpha and gamma interferon combined with the standard chemotherapeutic agents Taxol and Carboplatin results in increased killing of target tumor cells. We have shown that 10 ovarian cancer cell lines are sensitive to this treatment regimen. Furthermore, we have extended this observation to show that monocytes isolated from the whole blood of healthy donors are capable of killing cells in vitro. We have also performed an advanced microarray analysis of monocytes treated with the interferons to identify which protein(s) are mediating the in vivo cell death. The array has identified a number of target genes for validation and further study. We have been isolating monocytes from patients with ovarian cancer in collaboration with Dr. Annunziata. We have found that patient monocytes are as effective killers of ovarian cancer cell lines as healthy human age matched controls.