Preferred Label : 4H11-28z/fIL-12/EGFRt-expressing Autologous T-lymphocytes;
NCIt synonyms : 4H11-28z/fIL-12/EGFRt Genetically-modified T Cells; Autologous 4H11-28z/fIL-12/EGFRt Genetically-modified T Cells; Autologous MUC16ecto-targeting EGFR-secreting T Lymphocytes; 4H11-28z/fIL-12/EGFRt T Cells;
NCIt definition : A preparation of genetically modified autologous T-lymphocytes transduced with a retroviral
vector expressing a chimeric antigen receptor (CAR) targeting the human tumor-associated
antigen (TAA) MUC16ecto and encoding the human pro-inflammatory cytokine interleukin-12
(IL-12), fused to the signaling domain of the zeta chain of the TCR/CD3 complex (28z),
and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential
immunostimulating and antineoplastic activities. Upon intravenous administration,
4H11-28z/fIL-12/EGFRt-expressing autologous T-lymphocytes are directed to and induce
selective toxicity in MUC16-expressing tumor cells. In addition, the T-cells secrete
IL-12 which induces secretion of interferon-gamma, promotes the activation of natural
killer cells (NKs), and induces cytotoxic T-cell responses against tumor cells, which
may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation.
Devoid of both ligand binding domains and tyrosine kinase activity, the expressed
EGFRt both facilitates in vivo detection of the administered, transduced T-cells and
can promote elimination of those cells through a cetuximab-induced antibody-dependent
cellular cytotoxicity (ADCC) response. MUC16, a transmembrane protein and glycosylated
mucin, is overexpressed on the cell surface of the majority of ovarian cancer cells
but not on healthy cells. MUC16ecto is the extracellular portion of MUC-16 and is
the part that is retained by cells after cleavage of CA-125.;
Origin ID : C123823;
UMLS CUI : C4084782;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
