MHC-Restricted and MHC-Non-Restricted Targeting of Ovarian Cancer by alphaDC1

alphaDC1 对卵巢癌的 MHC 限制性和 MHC 非限制性靶向

• 批准号: 8485810
• 负责人: Pawel Kalinski
• 金额: $ 25.2万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485810
• 关键词: Antigens; Autologous Dendritic Cells; CD8B1 gene; CD94 Antigen; Cancer Patient; Dendritic Cell Vaccine; Epitopes; Genomic Instability; Goals; Immune; Immunosuppression; Immunotherapy; Infusion procedures; Malignant Neoplasms; Malignant neoplasm of ovary; Mutate; Patients; Recurrence; Residual Tumors; T-Lymphocyte; University of Pittsburgh Cancer Institute; Variant; cancer cell; chemotherapy; neoplastic cell; novel; outcome forecast; prevent; tumor

Genomic instability of ovarian cancer (OvCa) cells and the resulting frequent loss or reduction of HLA expression and function facilitate immune avoidance of this aggressive cancer. The goal of this Project is to develop an effective mode of immunotherapy capable of targeting both MHC-positive and MHC-negative variants of OvCa and counteracting local immune suppression, known to contribute to poor prognosis in OvCa patients. We observed that type-1-polarized DCs (¿DC1s), a novel type of DCs developed by our group, effectively cross-present OvCa-related antigens and induce high numbers of MHC class l-restricted CTLs capable of recognizing defined OvCa-related antigenic epitopes. However aDC1-induced CTLs also express elevated levels of NK receptors, NKG2D- and DNAM1. Such

卵巢癌（OvCa）细胞的基因组不稳定性和由此导致的HLA表达和功能的频繁丧失或降低促进了这种侵袭性癌症的免疫避免。该项目的目标是开发一种有效的免疫治疗模式，能够靶向OvCa的MHC阳性和MHC阴性变体，并抵消已知导致OvCa患者预后不良的局部免疫抑制。我们观察到，1型极化DC（µ DC 1 s）是我们小组开发的一种新型DC，它有效地交叉提呈OvCa相关抗原，并诱导大量能够识别特定OvCa相关抗原表位的MHC I类限制性CTL。然而，aDC 1诱导的CTL也表达升高水平的NK受体、NKG 2D-和DNAM 1。等