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

由于卵巢癌的高复发率和对常用化疗药物的耐药性，卵巢癌仍然是预后较差的妇科恶性肿瘤。因此，在目前的研究中，正在评估新的靶向治疗和免疫方法。卵巢癌患者非常适合腹腔免疫治疗，因为大多数患者患有腹膜癌和恶性腹水。近年来，以自然杀伤细胞（NK细胞）为基础的免疫治疗概念在卵巢癌的治疗中取得了可喜的成果，本课题旨在建立一种基于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的免疫修饰剂的整合和评估是该提案的一个关键方面。抗EGFR特异性纳米颗粒可能会改善肿瘤/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性因子（可能是免疫抑制因子）组成，我们还将研究腹水存在时肿瘤/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对卵巢癌的潜在疗效。

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.