Combining NK cells and mAb9.2.27 to combat NG2-dependent and anti-inflammatory signals in glioblastoma
نویسندگان
چکیده
Glioblastoma is a deadly brain cancer with limited treatment options. Targeting chondroitin sulfate proteoglycan 4 (CSPG4, best known as NG2) with the monoclonal antibody mAb9.2.27 and activated natural killer (NK) cells abrogated the tumor growth and prolonged the survival of glioblastoma-bearing animals by favoring the establishment of a pro-inflammatory microenvironment. The combination of NK cells and mAb9.2.27 recruited ED1+CCR2low macrophages that stimulated ED1+ED2lowMHCIIhigh microglial cells to exert robust cytotoxicity. Our findings demonstrate the therapeutic potential of targeting salient tumor associated-antigens.
منابع مشابه
Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival
Glioblastoma (GBM) is the most malignant brain tumor where patients' survival is only 14.6 months, despite multimodal therapy with debulking surgery, concurrent chemotherapy and radiotherapy. There is an urgent, unmet need for novel, effective therapeutic strategies for this devastating disease. Although several immunotherapies are under development for the treatment of GBM patients, the use of...
متن کاملDynamic Contrast Enhanced MRI Detects Early Response to Adoptive NK Cellular Immunotherapy Targeting the NG2 Proteoglycan in a Rat Model of Glioblastoma
There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast ...
متن کاملEffect of Soluble HLA Class I Molecule on NK/LAK Cells Activation Induced by Poly I:C
Background: Natural Killer cells express killer inhibitory receptors specific for HLA-class I molecules. These receptors could induce signals that determine NK cells ability to mediate cytotoxicity. Purified soluble form of HLA class I molecules (sHLA) could bind to NK cell receptors and down-regulate the NK killer function. Objective: To evaluate the influence of sHLA and two monoclonal an...
متن کاملKiller Cell Immunoglobulin-Like Receptors Influence the Innate and Adaptive Immune Responses
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibi...
متن کاملP157: Periostin Recruits Tumor Associated Macrophages in Glioblastoma Multiform
Glioblastoma multiform (GBM) is the most common and lethal type of primary brain tumors with high rates of morbidity and mortality. Treatment options are limited and ineffective in most of the cases. Epidemiological studies have shown a link between inflammation and glioma genesis. In addition, at the molecular level, pro-inflammatory cytokines released from activated microglia can increa...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 3 شماره
صفحات -
تاریخ انتشار 2014