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    1year
    EGFRvIII overexpression and loss of mouse specific CDKN2A in glial cells leads to gliomagenesis in a novel mouse model (SNO 2023)
    Xenograft tumors are reminiscent of the primary tumor, with similar histopathological features and immunohistochemical staining. This novel mouse model can be used to study diffuse glioma with a leptomeningeal component.
    Preclinical
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FAP (Fibroblast activation protein, alpha) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)
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    EGFR overexpression • CDKN2A deletion • EGFRvIII expression • EGFRVIII overexpression
    over2years
    Combination of EGFRvIII CAR T cell therapy and paracrine GAM modulation for the treatment of GBM (EANO 2022)
    Here, we show that EGFRvIII CAR T specifically targeted and killed EGFRvIII + GBM cells in vitro , but failed to control tumor growth in vivo without GAM modulation. EGFRvIII-SGRP CAR T secretome analysis identified SGRP from the supernatants of unstimulated monocultures. SGRP impaired the binding of SIRPα-Fc to CD47-upregulated GBM cells in vitro , but did not elicit macrophage-mediated phagocytosis of GBM cells in our current in vitro experimental setup.
    CAR T-Cell Therapy
    |
    CD19 (CD19 Molecule) • IFNG (Interferon, gamma) • CD47 (CD47 Molecule) • IL2RA (Interleukin 2 receptor, alpha) • LAMP1 (Lysosomal Associated Membrane Protein 1) • SIRPA (Signal Regulatory Protein Alpha)
    |
    EGFR overexpression • CD47 overexpression • IL2RA expression • EGFRvIII expression • EGFRVIII overexpression
    over2years
    TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo. (PubMed, Neuro Oncol)
    Our novel GBM models presented the growth advantage of heterozygous TPMs for the first time in the context of GBM driver mutations relative to isogenic controls, thereby allowing for the identification and validation of TERT promoter-specific vulnerabilities in a genetically accurate background.
    Preclinical • Journal
    |
    PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    PTEN deletion • PTEN mutation • EGFR overexpression • CDKN2A deletion • EGFRvIII expression • EGFRVIII overexpression
    3years
    Androgen Receptor Activation in Glioblastoma Can Be Achieved by Ligand-Independent Signaling through EGFR-A Potential Therapeutic Target. (PubMed, Int J Mol Sci)
    Afatinib diminished AKT phosphorylation at 30 min and 6 h in the EGFR- and EGFRvIII-overexpressing cells, respectively, and decreased AR phosphorylation in EGFR-overexpressing cells at 4 h. Afatinib or MK2206 combination therapy with the AR antagonist enzalutamide in the EGFR and EGFRvIII-overexpressing cells had synergistic efficacy. Our findings suggest that EGFR signaling is involved in AR activation in glioblastoma and buttresses the concept of combining an EGFR signaling inhibitor with AR antagonists as a potential glioblastoma treatment.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • AR (Androgen receptor)
    |
    EGFR overexpression • EGFRvIII expression • EGFRVIII overexpression
    |
    Gilotrif (afatinib) • Xtandi (enzalutamide) • MK-2206