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Exploring human T lymphocytes redirected to the tumor neoantigen EGFRvIII for adoptive cellular immunotherapy of non small cell lung cancer

Laufzeit: 01.01.2018 - 31.12.2019

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Kurzfassung


Adoptive cellular therapy (ACT) using CD19 chimeric-antigen-receptor (CAR) redirected T cells has shown remarkable results in acute and chronic B cell leukemias. However, in contrast to hematological malignancies, efficacy of ACT in solid tumors is often hampered by insufficient homing, persistence and nondurable immunity of T cells facing an immunosuppressive tumor microenvironment. Moreover, tumor-specific neoantigens to be targeted by CAR T cells with low adverse off-target effects are...Adoptive cellular therapy (ACT) using CD19 chimeric-antigen-receptor (CAR) redirected T cells has shown remarkable results in acute and chronic B cell leukemias. However, in contrast to hematological malignancies, efficacy of ACT in solid tumors is often hampered by insufficient homing, persistence and nondurable immunity of T cells facing an immunosuppressive tumor microenvironment. Moreover, tumor-specific neoantigens to be targeted by CAR T cells with low adverse off-target effects are difficult to identify.
The epithelial growth factor variant III (EGFRvIII) is only expressed in neoplasia, evaluated for CAR therapy in glioblastoma, and also found as CAR target in non small cell lung cancer (NSCLC). However, EGFRvIII-CAR modified T cells have not yet been extensively elaborated in NSCLC. Therefore, in this preclinical study we aim to evaluate antitumoral immunity of EGFRvIII-CAR T cells against NSLCL in vitro and in vivo using an NSG xenograft model.
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