Preferred Label : Autologous CISH-inactivated TILs;
NCIt synonyms : Autologous CISH-inactivated TIL; Autologous CISH-inactivated Tumor-infiltrating Lymphocytes; Autologous CISH-inactivated T-lymphocytes; Autologous CRISPR/Cas 9-CISH Knockout TILs;
NCIt definition : A preparation of autologous tumor-infiltrating lymphocytes (TILs) where the cytokine-inducible
SH2-containing protein gene (CISH) has been inactivated using the clustered regularly
interspaced short palindromic repeat (CRISPR)/CRISPR associated protein 9 (Cas9) editing
system, containing guide RNA (gRNA) coupled to a recombinant form of the DNA endonuclease
Cas9, with potential immunomodulating and antineoplastic activities. Using the CRISPR/Cas9
system, the autologous TILs are transfected, ex vivo, with a plasmid encoding for
a gRNA that site-specifically targets and binds to the human CISH gene. Cas9 cleaves
these specific DNA sites, which causes double strand breaks, disrupts the gene encoding
CISH and prevents transcription. Upon intravenous administration, the autologous CISH-inactivated
TILs are able to induce a T-cell-mediated immune response against tumor cells. CISH,
a member of the suppressor of cytokine signaling family (SOCS; cytokine-induced STAT
inhibitor; STAT-induced STAT inhibitor; SSI), is induced by T-cell receptor (TCR)
stimulation. CISH plays a key role in the negative regulation of both T-cell signaling
and CTL-mediated tumor cell eradication. The knockout of the CISH gene enhances the
expansion and anti-tumor activities of effector T-cells.;
NCI Metathesaurus CUI : CL553265;
Origin ID : C151926;
UMLS CUI : C4726557;
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
