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- NCIT_C148462 IAO_0000115 "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." @default.
- NCIT_C148462 NCIT_A32 NCIT_C1909 @default.
- NCIT_C148462 NCIT_A7 NCIT_C105113 @default.
- NCIT_C148462 NCIT_A7 NCIT_C17281 @default.
- NCIT_C148462 NCIT_NHC0 "C148462" @default.
- NCIT_C148462 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C148462 NCIT_P106 "Virus" @default.
- NCIT_C148462 NCIT_P107 "Double-armed TMZ-CD40L/4-1BBL Oncolytic Ad5/35 Adenovirus LOAd703" @default.
- NCIT_C148462 NCIT_P108 "Delolimogene Mupadenorepvec" @default.
- NCIT_C148462 NCIT_P208 "CL551080" @default.
- NCIT_C148462 NCIT_P210 "2061938-98-3" @default.
- NCIT_C148462 NCIT_P319 "3ZQ57V6YWZ" @default.
- NCIT_C148462 NCIT_P322 "CTRP" @default.
- NCIT_C148462 NCIT_P322 "FDA" @default.
- NCIT_C148462 NCIT_P322 "GDC" @default.
- NCIT_C148462 NCIT_P329 "802087" @default.
- NCIT_C148462 NCIT_P330 "802087" @default.
- NCIT_C148462 NCIT_P375 "Delolimogene Mupadenorepvec" @default.
- NCIT_C148462 NCIT_P375 "Double-armed TMZ-CD40L/4-1BBL Oncolytic Ad5/35 Adenovirus LOAd703" @default.
- NCIT_C148462 NCIT_P399 "802087" @default.
- NCIT_C148462 normalizedInformationContent "100" @default.
- NCIT_C148462 referenceCount "1" @default.
- NCIT_C148462 hasExactSynonym "DELOLIMOGENE MUPADENOREPVEC" @default.
- NCIT_C148462 hasExactSynonym "Delolimogene Mupadenorepvec" @default.
- NCIT_C148462 hasExactSynonym "LOAd 703" @default.
- NCIT_C148462 hasExactSynonym "LOAd-703" @default.
- NCIT_C148462 hasExactSynonym "LOAd703" @default.
- NCIT_C148462 hasExactSynonym "Oncolytic Adenovirus LOAd703" @default.
- NCIT_C148462 inSubset NCIT_C116977 @default.
- NCIT_C148462 inSubset NCIT_C116978 @default.
- NCIT_C148462 inSubset NCIT_C128784 @default.
- NCIT_C148462 inSubset NCIT_C157711 @default.
- NCIT_C148462 inSubset NCIT_C157712 @default.
- NCIT_C148462 inSubset NCIT_C176424 @default.
- NCIT_C148462 inSubset NCIT_C177537 @default.
- NCIT_C148462 inSubset NCIT_C63923 @default.
- NCIT_C148462 type Class @default.
- NCIT_C148462 isDefinedBy ncit.owl @default.
- NCIT_C148462 label "Delolimogene Mupadenorepvec" @default.
- NCIT_C148462 subClassOf NCIT_C129821 @default.
- NCIT_C148462 subClassOf NCIT_C148462 @default.
- NCIT_C148462 subClassOf NCIT_C1908 @default.
- NCIT_C148462 subClassOf NCIT_C1909 @default.
- NCIT_C148462 subClassOf NCIT_C1962 @default.
- NCIT_C148462 subClassOf NCIT_C274 @default.
- NCIT_C148462 subClassOf NCIT_C307 @default.
- NCIT_C148462 subClassOf NCIT_C717 @default.