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The vector of anti-EGFRvIII chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human EGFRvIII. The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-EGFRvIII antibody linked to 41BB and CD3ζ signaling domains. And the vector product was designed for the treatment of Human glioblastoma (GBM).
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CAR Construction :
Fig.1 VM/Dk-derived glioma SMA560vIII shows EGFRvIII expression compared with SMA560 by surface antibody staining (L8A4) and flow cytometry EGFRvIII mCAR retroviral gene delivery to murine T cells confers antigen-specific activity. Sampson, J. H., Choi, B. D., Sanchez-Perez, L., Suryadevara, C. M., Snyder, D. J., Flores, C. T., ... & Johnson, L. A. (2014). EGFRvIII mCAR-Modified T-Cell Therapy Cures Mice with Established Intracerebral Glioma and Generates Host Immunity against Tumor-Antigen LossEGFRvIII mCARs for Malignant Glioma. Clinical Cancer Research, 20(4), 972-984. |
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CAR Construction :
Fig.2 SMA560 (EGFRvIIINEG) gliomas were maintained in vitro or passaged in a mouse subcutaneously for 14 days, then harvested and both were stained for EGFRvIII expression using L8A4 mAb and analyzed by flow cytometry. Treatment of mice bearing EGFRvIIIPOS tumors with mCARs provides long-term protection against EGFRvIIINEG tumor. Sampson, J. H., Choi, B. D., Sanchez-Perez, L., Suryadevara, C. M., Snyder, D. J., Flores, C. T., ... & Johnson, L. A. (2014). EGFRvIII mCAR-Modified T-Cell Therapy Cures Mice with Established Intracerebral Glioma and Generates Host Immunity against Tumor-Antigen LossEGFRvIII mCARs for Malignant Glioma. Clinical Cancer Research, 20(4), 972-984. |
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