Preferred Label : Allogeneic CRISPR-edited Anti-CLL-1 CAR-T Cells CB-012;
NCIt synonyms : Allogeneic Anti-CLL-1 CAR T-cells CB-012; Allogeneic Anti-CLL-1 CAR T Cells CB-012;
NCIt definition : A preparation of allogeneic, off-the-shelf T-lymphocytes genetically modified and
clustered regularly interspaced short palindromic repeats (CRISPR)-edited to contain
the deletion of the TRAC gene, the site-specific insertion of a chimeric antigen receptor
(CAR) specific for the tumor-associated antigen (TAA) C-type-lectin-like molecule-1
(CLL-1; CLL1; C-type lectin domain family 12 member A; CLEC12A; CD371) into the TRAC
gene, the knockout of programmed death 1 (PD-1; PDCD1; CD279; programmed cell death-1),
the deletion of the B2M gene, and the site-specific insertion of a gene encoding a
B2M-HLA-E-peptide fusion into the B2M gene, with potential immunostimulating and antineoplastic
activities. Upon administration, allogeneic CRISPR-edited anti-CLL-1 CAR-T cells CB-012
recognize and bind to CLL-1-expressing tumor cells. This may result in a specific
cytotoxic T-lymphocyte (CTL)-mediated killing of CLL-1-expressing tumor cells. Knock
out of the TRAC gene eliminates the endogenous T-cell receptors (TCRs), thereby preventing
graft-versus-host disease (GvHD). PD-1, an immune checkpoint receptor expressed on
T-cells, plays a key role in tumor immune evasion by binding to its ligand programmed
death ligand 1 (PD-L1; cluster of differentiation 274; CD274; programmed cell death-1
ligand 1) expressed on tumor cells. By removing PD-1 from T-cells, PD-1-mediated signaling
is halted which may decrease T-cell exhaustion and may enhance T-cell activity against
the CLL-1-expressing tumor cells. The B2M protein is removed to eliminate endogenous
HLA class I expression on the surface of the CB-012 CAR-T cells, which protects the
CAR-T cells from host T-cell rejection. The B2M-HLA-E fusion protein is inserted to
protect the CAR-T cells from host natural killer (NK) cell rejection. CLL-1, a member
of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily, is overexpressed
in leukemic stem cells (LSCs) and plays an important role in disease progression and
relapse for myeloid malignancies.;
Molecule name : CB-012; CB 012;
NCI Metathesaurus CUI : CL1926335;
Origin ID : C204039;
UMLS CUI : C5908021;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
- has_target
