Preferred Label : Delolimogene Mupadenorepvec;
NCIt synonyms : Oncolytic Adenovirus LOAd703;
NCIt definition : A double-armed oncolytic adenovirus composed of a recombinant genetically modified
E1/E3-deleted, adenoviral serotype 5 (Ad5) vector, with the L5 segment of the Ad5
fiber replaced by the shaft and knob from the Ad35 serotype (Ad5/35), which expresses
a trimerized (TMZ) form of the membrane-bound immunostimulator CD40 ligand (CD40L;
TNFSF5) and the ligand for the signaling domain 4-1BB (4-1BBL; CD137L; TNFSF9), under
the control of a CMV promoter, with potential immunostimulating and antineoplastic
activities. Upon intratumoral administration of delolimogene mupadenorepvec, the virus
infects and selectively replicates in tumor cells. This causes direct oncolysis and
the release of a plethora of tumor-associated antigens (TAAs) from the tumor cells.
The released TAAs stimulate the immune system and activate anti-tumor cytotoxic T-lymphocytes
(CTLs), thereby further killing tumor cells. In addition, infected tumor cells and
tumor stroma cells, including stellate cells and infiltrating immune cells, express
the immunostimulants CD40L and 4-1BBL. The expressed CD40L and 4-1BBL proteins activate
the CD40L- and 4-1BBL-mediated signaling pathways, respectively. This activates antigen-presenting
cells (APCs), such as dendritic cells (DCs) and M1 macrophages. The DCs produce various
cytokines, including interleukin-12 (IL12), IL21, tumor necrosis factor-alpha (TNFa),
and interferon-gamma (IFNg), which leads to the activation and expansion of both T-cells
and natural killer (NK) cells. Altogether, this modulates immune suppression in the
tumor microenvironment (TME), disrupts tumor stroma, and causes additional immune
stimulation against tumor cells, thereby inducing further tumor cell lysis. In addition,
CD40L reduces myeloid suppressor cells in the TME. Inclusion of the chimeric Ad5/35
fiber targets CD46 and increases viral uptake in cells. Transgene expression is driven
by a separate promoter to allow for efficient expression in both tumor cells and tumor
stroma. Replication is restricted to tumor cells by the presence of the delta24 mutation
in the E1A gene, which deletes the retinoplastoma protein (pRb)-binding domain and
forces viral replication to be conditional on hyperphosphorylated pRb and a dysfunctional
Rb pathway.;
UNII : 3ZQ57V6YWZ;
CAS number : 2061938-98-3; a href https://gsrs.ncats.nih.gov/ginas/app/beta/browse-substance?search 2061938-98-3
alt lien vers site G-SRS target _blank img src /img/logos/logo_g-srs.png alt Logo
G-SRS /a ;
Molecule name : LOAd-703; LOAd 703;
NCI Metathesaurus CUI : CL551080;
Origin ID : C148462;
UMLS CUI : C4725049;
Semantic type(s)
- concept_is_in_subset
- has_target
