Mechanisms of Antitumor Action of Human Interferon

人干扰素的抗肿瘤作用机制

• 批准号: 8946434
• 负责人: Kathryn Zoon
• 金额: $ 20.03万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8946434
• 关键词: Age; Cancer cell line; Carboplatin; Cell Death; Cell Therapy; Coculture Techniques; Collaborations; Diagnosis; Disease; Disease remission; Gene Targeting; Goals; Greater sac of peritoneum; Human; Immune; In Vitro; Interferon Type II; Interferon-alpha; Interferons; Malignant neoplasm of ovary; Mediating; Metastatic Lesion; Microarray Analysis; Neoplasm Metastasis; Operative Surgical Procedures; Ovary; Paclitaxel; Patients; Primary Neoplasm; Proteins; Resistance; Treatment Protocols; Tumor Debulking; Validation; Whole Blood; base; cell killing; chemotherapeutic agent; chemotherapy; in vivo; killings; monocyte; mortality; neoplastic cell; ovarian neoplasm

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.

我们现在已经证明，干扰素α和γ引发的单核细胞的共培养能够在体外和体内杀死卵巢肿瘤细胞，并且两种干扰素的存在对于杀肿瘤作用是必要的。此外，我们还表明，用α和γ干扰素与标准化疗药物紫杉醇和卡铂联合引发的单核细胞可增加对靶肿瘤细胞的杀伤力。我们已经证明 10 种卵巢癌细胞系对此治疗方案敏感。此外，我们还扩展了这一观察结果，表明从健康捐献者的全血中分离出的单核细胞能够在体外杀死细胞。我们还对用干扰素处理的单核细胞进行了先进的微阵列分析，以确定哪些蛋白质介导体内细胞死亡。该芯片已鉴定出许多目标基因用于验证和进一步研究。我们一直与 Annunziata 博士合作从卵巢癌患者身上分离单核细胞。我们发现，患者单核细胞与健康人类年龄匹配的对照一样，是卵巢癌细胞系的有效杀手。