Preferred Label : TSP-1 Activator VT1021;
NCIt synonyms : Thrombospondin 1 Activator VT1021;
NCIt definition : A cyclic pentapeptide and stimulator of thrombospondin 1 (TSP-1; THBS1), with potential
anti-angiogenic, immunomodulating and antineoplastic activities. Upon administration,
TSP-1 activator VT1021 specifically stimulates TSP-1 expression in inflammatory myeloid-derived
suppressor cells (MDSCs) in the tumor microenvironment (TME), which binds to TSP-1
receptors, mainly CD36 and CD47. This activates CD36-mediated signaling and induces
apoptosis in tumor and endothelial cells, which may result in the inhibition of tumor
cell proliferation. The binding of TSP-1 to CD47 prevents the interaction between
CD47 and the signal regulatory protein alpha (SIRPalpha; SIRPa) that is expressed
on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the
CD47/SIRPa-mediated inhibition of macrophage activation and phagocytosis of cancer
cells. In addition, VT1021 can reprogram the immunosuppressive TME, skewing macrophages
from the immune suppressive M2 phenotype to an effector M1 phenotype, increasing the
infiltration of cytotoxic T-lymphocytes (CTLs) while decreasing regulatory T-cells
(Tregs) in the TME, thereby stimulating an anti-tumor immune response and further
killing tumor cells.;
Molecule name : VT-1021; VT 1021;
Origin ID : C210747;
concept_is_in_subset
- has_target
