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- NCIT_C168607 IAO_0000115 "A replication competent, oncolytic adenovirus serotype 5 (Ad5) that has been modified with a delta24 (d24) deletion, an incorporation of an RGD-4C motif in the Ad fiber protein, and an insertion of the T1 mutation in E3/19K gene, with potential oncolytic activity. Upon administration, oncolytic adenovirus ORCA-010 binds to specific Ad3 receptors that are highly expressed on certain tumor cells. This results in the replication of oncolytic adenovirus Ad5/3-delta24 in tumor cells and induces tumor cell lysis which may potentially result in the activation of a systemic immune response against tumor-associated antigens (TAAs). The Ad5/3-delta24 has a 24 base pair deletion in constant region 2 of the E1A gene which allows for selective replication in cells that are defective in the retinoblastoma gene (Rb) or cyclin-dependent kinase inhibitor-2A (CDKN2A or p16INK4a). As most tumor cells are defective in the Rb/p16 pathway, this virus selectively replicates in these cells. The RGD-4C motif is a 9-amino acid peptide that binds to various and enhances viral-cell receptor binding by allowing for a Coxsackie-adenovirus receptor (CAR)-independent infection of tumor cells, which is the natural route of viral binding, as CAR expression is often deficient on cancer cells. As integrins are often overexpressed on tumor cell surfaces, integrin receptor binding enhances tumor cells binding and infection by the Ad. The T1 mutation enhances the Ad5 release from tumor cells and promotes spreading throughout the tumor, thereby enhancing anti-tumor activity. The T1 mutation, a single Adenine insertion at position 445 of the nucleotide sequence of the E3/19K gene of Adenovirus, creates a truncated E3/19K protein that is relocated to the plasma membrane due to the disruption of its ER retention signal. This increases plasma membrane permeability and enhances the release of Ad5." @default.
- NCIT_C168607 NCIT_A32 NCIT_C1909 @default.
- NCIT_C168607 NCIT_NHC0 "C168607" @default.
- NCIT_C168607 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C168607 NCIT_P106 "Virus" @default.
- NCIT_C168607 NCIT_P108 "Oncolytic Adenovirus ORCA-010" @default.
- NCIT_C168607 NCIT_P208 "CL972811" @default.
- NCIT_C168607 NCIT_P322 "GDC" @default.
- NCIT_C168607 NCIT_P329 "800320" @default.
- NCIT_C168607 NCIT_P330 "800320" @default.
- NCIT_C168607 NCIT_P375 "Oncolytic Adenovirus ORCA-010" @default.
- NCIT_C168607 NCIT_P399 "800320" @default.
- NCIT_C168607 normalizedInformationContent "100" @default.
- NCIT_C168607 referenceCount "1" @default.
- NCIT_C168607 hasExactSynonym "Modified Ad5 ORCA-010" @default.
- NCIT_C168607 hasExactSynonym "ORCA 010" @default.
- NCIT_C168607 hasExactSynonym "ORCA-010" @default.
- NCIT_C168607 hasExactSynonym "ORCA010" @default.
- NCIT_C168607 hasExactSynonym "Oncolytic Adenovirus ORCA-010" @default.
- NCIT_C168607 inSubset NCIT_C128784 @default.
- NCIT_C168607 inSubset NCIT_C157711 @default.
- NCIT_C168607 inSubset NCIT_C157712 @default.
- NCIT_C168607 inSubset NCIT_C176424 @default.
- NCIT_C168607 inSubset NCIT_C177537 @default.
- NCIT_C168607 type Class @default.
- NCIT_C168607 isDefinedBy ncit.owl @default.
- NCIT_C168607 label "Oncolytic Adenovirus ORCA-010" @default.
- NCIT_C168607 subClassOf NCIT_C129821 @default.
- NCIT_C168607 subClassOf NCIT_C168607 @default.
- NCIT_C168607 subClassOf NCIT_C1908 @default.
- NCIT_C168607 subClassOf NCIT_C1909 @default.
- NCIT_C168607 subClassOf NCIT_C274 @default.
- NCIT_C168607 subClassOf NCIT_C307 @default.
- NCIT_C168607 subClassOf NCIT_C717 @default.