Preferred Label : Oncolytic Adenovirus ORCA-010;
NCIt synonyms : Modified Ad5 ORCA-010;
NCIt definition : 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.;
Molecule name : ORCA 010; ORCA-010;
NCI Metathesaurus CUI : CL972811;
Origin ID : C168607;
UMLS CUI : C5238979;
Semantic type(s)
- Virus [UMLS semantic type]
- concept_is_in_subset
