Preferred Label : Surface-engineered Lentiviral Particles-expressing Cocal Glycoprotein/Anti-CD3 scFv
Containing Transgene Encoding for Anti-CD19 CAR/Rapamycin Activated Cytokine Receptor
System UB-VV111;
NCIt synonyms : Gene Therapy Agent UB-VV111; Surface-engineered Lentiviral Particles Containing Transgene Encoding for Anti-CD19
CAR/Rapamycin Activated Cytokine Receptor System UB-VV111; VivoVec-based Lentiviral Particles UB-VV111; Surface-engineered Lentiviral Particles Containing Transgene Encoding for Anti-CD19
CAR/RACR System UB-VV111; Lentiviral Vector-based Gene Therapy Agent UB-VV111;
NCIt definition : A particles-based gene therapy agent composed of a surface-engineered self-inactivating
replication-incompetent lentiviral envelope expressing the cocal fusion glycoprotein
and an anti-CD3 single chain variable fragment (scFv) and encapsulating a transgene
encoding for a chimeric antigen receptor (CAR) that targets the tumor-associated antigen
(TAA) CD19 and a rapamycin activated cytokine receptor (RACR), with potential to in
vivo generate anti-CD19 CAR T-cells that may have immunostimulating and antineoplastic
activities. The RACR system contains a FKBP12-rapamycin-binding protein (FRB) and
a chimeric heterodimer cytokine receptor consisting of RACRgamma, which is composed
of an FKBP extracellular unit attached to an interleukin-2 receptor gamma (IL-2Rgamma)
signaling domain, and RACRbeta, which is composed of an FRB extracellular unit attached
to an IL-2Rbeta signaling domain. Upon administration of the surface-engineered lentiviral
particles-expressing cocal glycoprotein/anti-CD3 scFv containing transgene encoding
for anti-CD19 CAR/RACR system UB-VV111, the anti-CD3 scFv and cocal glycoprotein mediate
CD3-positive T-cell binding, activation and T-cell transduction. Upon transduction,
the T-cells express an anti-CD19 CAR and the RACR system. These in vivo generated
anti-CD19 CAR T-cells induce cytokine production, proliferate and kill CD19-expressing
tumor cells. Upon administration of rapamycin (sirolimus), rapamycin binds to RACR,
which allows heterodimerization of the FKBP-interleukin (IL)-2Rgamma fusion with the
FRB-IL-2Rbeta fusion, and results in intracellular IL-2- and IL-15-mediated signaling
and promotes proliferation and persistence of the UB-VV111 engineered CAR T-cells.
The FRB domain binds to intracellular rapamycin-FKBP12 complexes and thereby prevents
the binding of the intracellular rapamycin-FKBP12 complexes to rapamycin-mediated
mammalian target of rapamycin (mTOR) and inhibits the activity of mTOR. This protects
against mTOR-mediated and immune-mediated removal of the CAR T-cells and increases
their survival. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell
lineage tumors.;
Molecule name : UB VV111; UB-VV111;
Origin ID : C211928;
concept_is_in_subset
