Szerző szerinti böngészés "Medyouni, Ghofrane"

Megjelenítve 1 - 5 (Összesen 5)
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    TételSzabadon hozzáférhető
    Activity of Potassium Channels in CD8+ T Lymphocytes: diagnostic and Prognostic Biomarker in Ovarian Cancer?
    (2024) Jusztus, Vivien; Medyouni, Ghofrane; Bagosi, Adrienn; Lampé, Rudolf; Panyi, György; Matolay, Orsolya; Maka, Eszter; Krasznai, Zoárd Tibor; Vörös, Orsolya; Hajdu, Péter
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    TételKorlátozottan hozzáférhető
    Functional role of Kv1.3 localization in CAR-T cells
    (2025) Medyouni, Ghofrane; Vörös, Orsolya; Panyi, György; Hajdu, Péter
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    TételKorlátozottan hozzáférhető
    Generation of CAR-T cell lines
    Lima de Souza Pinto, Maria Eduarda; Medyouni, Ghofrane; Hajdu, Péter Béla; DE--Természettudományi és Technológiai Kar--Biotechnológiai Intézet
    Many forms of hematological malignancies as well as solid tumours can be treated using cellular immunotherapy, such as CAR-T, a treatment using T cells that express an antibody-based chimeric antigen receptor targeting tumor antigen. Due to the current challenges related to CAR-T cell therapy, as well as to investigate the potential of third-generation CARs, this study aimed to generate CAR-T cells by retroviral transduction and its sorting based on sGFP expression though Fluorescence-Activated Cell Sorting (FACS). The results obtained with flow cytometry analysis demonstrated approximately 52% of transduction efficiency. The confocal microscopy was able to detect sGFP signal, assessing the cellular distribution of sGFP-tagged CARs. The transduced cells were sorted using Fluorescence-Activated Cell Sorting (FACS) method. At the end of the process, one tube was obtained containing Jurkat cells highly expressing sGFP, corresponding to 46% of the original population.
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    TételSzabadon hozzáférhető
    Inhibition of K+ Channels Affects the Target Cell Killing Potential of CAR T Cells
    (2024) Medyouni, Ghofrane; Vörös, Orsolya; Jusztus, Vivien; Panyi, György; Vereb, György; Szöőr, Árpád; Hajdu, Péter
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    TételSzabadon hozzáférhető
    Role of ions channels in CAR-T cells
    (2025) Medyouni, Ghofrane; Hajdu Béla, Péter; Molekuláris orvostudomány doktori iskola; Általános Orvostudományi Kar::Biofizikai és Sejtbiológiai Intézet; Általános Orvostudományi Kar::Biofizikai és Sejtbiológiai Intézet::Biofizikai Tanszék
    T cell ion channels (Kv1.3, KCa3.1 and CRAC) regulate the activation and effector functions via modulating the Ca2+-dependent pathway. Chimeric antigen receptor (CAR T cell therapy) showed a remarkable success in anti-tumor therapy, especially in the treatment of chemotherapy-resistant liquid cancers. Nevertheless, the mechanisms regulating CAR-T cell function as well as the side effects remain an area of active research.In our research study, we assessed the expression and role of ion channels in CAR T cells using a Jurkat-cell model and in primary T cells. Our results from molecular, electrophysiological and functional assays highlight that the KCa3.1 conductance in HER2-specific CAR T cells was higher compared to the non-transduced (NT, control) cells, which was more prominent in the CD8+ population (CD4+ cell also showed elevation). The Kv1.3 expression level was the same for all cell types (CD4+, CD8+, CAR, and NT). Single-cell Ca2+ imaging revealed that thapsigargin-induced SOCE via CRAC is suppressed in CD8+ CAR T cells, unlike for CD4+ and CD8+ NT cells. The use of specific antagonists (Kv1.3: Vm24; KCa3.1: TRAM-34): showed that the target cell elimination capacity of the CD8+ CAR T cells was improved either by blocking KCa3.1 or Kv1.3.By means of our Jurkat-CAR cell line we could show that Kv1.3 channels is colocalized with CAR and redistributes into the synapse between a CAR and a target cell. The biophysical properties of Kv1.3 channel are not vastly affected by the introduction of CAR in the cells when Kv1.3 is the only expressed channel. The blockage of Kv1.3 channel lateral movement to the synapse affects the killing potential of CAR-T cells, likely through disruption of the Ca2+-response upon IS formation. Overall, these data suggest that the manipulation of the Kv1.3 channel may contribute to the improvement of CAR-T immunotherapy and provide new insights for future clinical strategies.