Attenuated Live Listeria monocytogenes Encoding KRAS G12D - CISMeF
Attenuated Live Listeria monocytogenes Encoding KRAS G12DNCIt concept
Preferred Label : Attenuated Live Listeria monocytogenes Encoding KRAS G12D;
NCIt synonyms : ADXS 503; Lm-Hot KRAS G12D;
NCIt definition : An off-the-shelf, plasmid DNA-based cancer vaccine composed of a live-attenuated strain
of the Gram-positive bacterium Listeria monocytogenes (Lm) carrying a plasmid vector
encoding multiple, not yet disclosed, tumor associated antigens (TAAs) and sequence
peptides associated with commonly occurring hotspot mutations, including the aspartic
acid substitution for glycine at position 12 (G12D) in KRAS, with potential immunostimulatory
and antineoplastic activities. Upon administration, ADXS-503 is taken up by antigen
presenting cells (APCs) and the TAAs are processed and presented to immune cells by
both major histocompatibility complex (MHC) I and II molecules. This leads to an increase
in antigen-specific CD8-positive T-cells and gamma/delta T-cells within the tumor
microenvironment (TME) and an inhibition of immunosuppressive tumor-infiltrating T-regulatory
cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This may lead to tumor
cell death in cells expressing TAAs that are shared across multiple tumor types. The
KRAS G12D mutation is thought to drive tumorigenesis and progression in some cancers.;