Table 2. Common cellular targets utilized in recent clinical trials for PDAC cancer vaccine.
Cellular targets | Rationale | References |
---|---|---|
Telomerase | Enzyme that is reactivated during oncogenic transformation Prevents the naturally occurring shortening of the telomeric ends of DNA during replication, which would lead to cell senescence and eventually cell death |
(82-84) |
Wilms tumor gene (WT1) | Identified on the cell surface of several cancerous cells including pancreatic cancer cells Highly immunogenic, eliciting both humoral and cellular responses |
(53,85-91) |
KIF20A (RAB6KIFL) | Member of the kinesin superfamily of motor proteins, that has a paramount role in the intracellular trafficking of molecules and organelles during the growth of pancreatic cancer | (54) |
Alpha-galactosyl (α-Gal) epitope | Human cells do not present the α-Gal epitope and on the contrary the anti-Gal antibody is abundant in human serum (about 1% of circulating human antibody) Genetically modified tumor cells that express α-Gal in addition to TAAs, in an attempt to induce a complement and antibody-dependent cell-mediated hyperacute rejection that would favor the processing and presentation of TAAs |
(76,92-95) |
Survivin (also known as baculoviral inhibitor of apoptosis repeat-containing 5; BIRC5) | Member of the inhibitor apoptosis protein (IAP) that is highly expressed in neoplastic tissues but absent in non-neoplastic human cells | (75,96-98) |
Mutated Ras protein | Derives from the Ki-Ras p21 oncogene and is expressed in cancer derived from different histologies and in approximately 90% of PDAC cases A point mutation at codon 12 results in specific substitution of a normal glycine (Gly) amino acidswith an aspartic acid (Asp), valine (Val), cysteine (Cys), or arginine (Arg) which can easily be targeted by a formulation of four different vaccines |
(58,99) |
Human mucin MUC1 protein | This protein is specifically expressed on the surface of pancreatic cancer cells and can be used as a specific tumor associated antigen (TAA) | (48,59,71,100) |
Vascular endothelial growth factor receptor 2 (VEGFR2) | VEGFR2 is highly expressed on endothelial cells of tissues undergoing a process of tumor-induced neovascularization but it is absent in normal blood vessels VEGFR2 has been identified on PDAC cancer cells Vaccination leads to the generation of CTL able to interfere with the processes associated with PDAC neovascularization. In addition, specific-CTLs have the potential to target PDAC cancer cells directly |
(61,101-103) |
Mesothelin | Overexpressed in most PDAC Participate in cell adhesion and has a potential role in metastatic progression |
(104) |
Personalized peptide vaccination (PPV) | Relatively new strategy of peptide-based vaccination The peptide utilized is chosen from a number of different pooled peptides and selected based on the patient’s HLA-class IA types and levels of peptide-specific IgG responses prior to vaccination |
(55,62,68) |