Preclinical development of a NK cell-based immunotherapy for ovarian cancer by anti-EGFR-agents and immune-nanoparticles

通过抗 EGFR 药物和免疫纳米颗粒进行基于 NK 细胞的卵巢癌免疫疗法的临床前开发

• 批准号: 394480033
• 负责人: Professor Dr. Sven Brandau
• 金额: --
• 依托单位: Klinik für Hals-Nasen-Ohrenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/394480033?language=en
• 关键词: Preclinical; development; NK; cell; based

Due to high recurrence rate and resistance to common chemotherapeutic agents ovarian cancer remains a gynecological malignancy with worse prognosis. Thus, in current studies novel targeted therapies and immunotherapeutic approaches are being evaluated. Ovarian cancer patients are well suited for intraperitoneal immunotherapy since most patients suffer from peritoneal carcinosis and malignant ascites. Recent immunotherapeutic concepts based on natural killer cells (NK cells) showed promising results in this tumour entity.The aim of this project is to establish a NK cell-based immunotherapeutic model for ovarian carcinoma. For stimulation of NK cell-activity anti-EGFR-specific therapeutic agents will be used. The integration and evaluation of biocompatible calciumphosphate-nanoparticles as potential immune modifiers represents a key aspect in this proposal. Anti-EGFR-specific nanoparticles might improve tumour-/NK cell-interaction and might serve as carriers for further immune stimulating substances such as siRNA. As malignant ascites consists of proinflammatory, presumably immunosuppressive factors, we will also investigate tumour-/NK cell-interaction in the presence of ascitic fluid. This project will contribute to a better understanding of the potential efficacy of an intraperitoneal cellular immunotherapy for ovarian cancer.

由于复发率高和对常用化疗药物耐药，卵巢癌仍然是预后较差的妇科恶性肿瘤。因此，在当前的研究中，正在评估新的靶向疗法和免疫治疗方法。卵巢癌患者非常适合腹腔内免疫治疗，因为大多数患者患有腹膜癌和恶性腹水。最近基于自然杀伤细胞（NK 细胞）的免疫治疗概念在这种肿瘤实体中显示出有希望的结果。该项目的目的是建立基于 NK 细胞的卵巢癌免疫治疗模型。为了刺激 NK 细胞活性，将使用抗 EGFR 特异性治疗剂。生物相容性磷酸钙纳米颗粒作为潜在免疫调节剂的整合和评估是该提案的一个关键方面。抗 EGFR 特异性纳米粒子可能会改善肿瘤/NK 细胞的相互作用，并可能作为进一步免疫刺激物质（如 siRNA）的载体。由于恶性腹水由促炎因子（可能是免疫抑制因子）组成，因此我们还将研究腹水存在下肿瘤/NK 细胞的相互作用。该项目将有助于更好地了解腹膜内细胞免疫疗法治疗卵巢癌的潜在功效。