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以及HLA表达和功能的经常丧失或减少，避免了这种攻击性癌症的免疫原子。该项目的目的是开发一种有效的免疫疗法模式，能够靶向OVCA的MHC阳性和MHC阴性变体，并抵消局部免疫抑制，已知会导致OVCA患者的预后不良。我们观察到我们组开发的一种新型的DC，有效地交叉OVCA相关的抗原，并影响大量的MHC类L限制的CTL，能够识别已定义的OVCA相关抗相关抗原性表位。但是，ADC1诱导的CTL也表达了NK受体NKG2D-和DNAM1的水平升高。这样的