Preferred Label : Oncolytic Herpes Simplex Virus-1 Expressing Anti-CTLA-4 Antibody/CD40L/4-1BBL RP3;
NCIt synonyms : Oncolytic HSV-1 Expressing Anti-CTLA-4 Antibody/CD40L/4-1BBL RP3;
NCIt definition : A genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1)
virus, expressing an antibody directed against the human inhibitory T-cell-expressed
receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4;CTLA4), CD40 ligand (CD40L;
CD154; TRAP; TNFSF5) and the co-stimulatory molecule tumor necrosis factor ligand
superfamily (TNFSF) member 9 (TNFSF9; 4-1BBL) with potential oncolytic, immunostimulating
and antineoplastic activities. Upon administration, the oncolytic HSV-1 expressing
anti-CTLA-4 Antibody/CD40L/4-1BBL RP3 specifically infects and replicates in tumor
cells causing viral-mediated tumor cell lysis. The released virus particles, in turn,
infect and replicate in neighboring tumor cells. Tumor antigens released from the
lysed tumor cells also activate the immune system to induce a tumor-specific systemic
immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected
tumor cells. Oncolytic virus RP3 expresses a fusogenic protein, GALV-GP R-, for optimal
tumor cell infection and killing. In addition, Oncolytic virus RP3 promotes the expression
of anti-CTLA-4 antibody, CD40L and 4-1BBL by the tumor cells. Anti-CTLA-4 antibody
targets and binds to CTLA-4 expressed on T-cells, and inhibits the CTLA-4-mediated
downregulation of T-cell activation. This leads to a CTL-mediated immune response
against tumor cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin
superfamily (IgSF), plays a key role in the downregulation of the immune system. CD40L
specifically binds to and activates CD40, a cell surface receptor that belongs to
the tumor necrosis factor (TNF) receptor family and is expressed on various immune
cells, such as B-lymphocytes, monocytes, and dendritic cells (DCs). Activation of
CD40 induces proliferation and activation of B-lymphocytes, shifts the induction of
suppressive macrophages towards immunostimulatory macrophages, activates monocyte-derived
DCs (moDCs), and leads to the secretion of inflammatory cytokines, which activates
the immune system to induce the proliferation and activation of CTLs against tumor
cells. 4-1BBL binds to and subsequently induces the proliferation and activation of
natural killer (NK) cells and T-cells. This enhances the secretion of cytokine interferon-gamma
(IFN-g) and further induces an anti-tumor immune response.;
Molecule name : RP-3; RP 3;
NCI Metathesaurus CUI : CL1663139;
Origin ID : C179624;
UMLS CUI : C5553010;
Semantic type(s)
- concept_is_in_subset
