Autologous TGFbeta-Resistant HER2/EBV-Specific Cytotoxic T Lymphocytes - CISMeF
Autologous TGFbeta-Resistant HER2/EBV-Specific Cytotoxic T LymphocytesNCIt concept
Preferred Label : Autologous TGFbeta-Resistant HER2/EBV-Specific Cytotoxic T Lymphocytes;
NCIt definition : A preparation of transforming growth factor-beta (TGF-beta)-resistant Epstein-Barr
virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) directed to EBV through their
native receptor and HER2 through a retrovirally transduced HER2 chimeric antigen receptor
(CAR) with potential antineoplastic activity. Autologous EBV-specific CTLs are produced
by exposing autologous CTLs to stimulator autologous EBV-transformed lymphoblastoid
cell lines (EBV-LCLs). Subsequently, autologous EBV-specific CTLs are transduced with
retroviral vectors expressing the mutant type II TGF-beta dominant-negative receptor
(DNR), which blocks signaling by all three TGF-beta isoforms, and the HER2 CAR. After
transduction, transgenic EBV-CTLs are expanded on EBV-LCLs. Upon administration, autologous
HER2 chimeric receptor/TGFbeta dominant negative receptor-expressing EBV-specific
cytotoxic T lymphocytes may bind to HER2-expressing tumors cells, which may result
in CTL-mediated cell lysis and inhibition of tumor cell proliferation. Tumor-expressed
TGF-beta inhibits T lymphocyte activation and expansion.;