245tissues where they present antigens to T cells and induce an immune response.
Dendritic cells can be derived from CD34+ precursors in response to granulocyte
macrophage colony stimulating factor and tumor necrosis factor and from mono-
cytes cultured with granulocyte macrophage colony stimulating factor and interleu-
kin- 4. DCs have the capacity to prime tumor-specifi c T cell responses and are
considered to be potentially effective vaccines for immunotherapy of cancer.
Various approaches for ex vivo loading of DCs with tumor-specifi c antigens
include tumor-derived peptide/protein, RNA/DNA, necrotic tumor cells, chaperone
proteins, exosomes, and or tumor cell-DC fusion (Janikashvili et al. 2010 ). DCs
may be administered intravenously, intradermally, subcutaneously or by intranodal
or intratumoral injection.
DCVax (Northwest Biotherapeutics) is a personalized therapeutic cancer vaccine
manufactured from the patient’s own DCs that have been modifi ed to teach the
immune system to recognize and kill cancer cells bearing the biomarker of patient’s
tumor. Published clinical trials of DC vaccine for high-grade glioma patients sug-
gest favorable clinical outcomes with evidence of low toxicity in effective induction
of antitumor immunity correlating with clinical improvement (Wheeler and Black
2009 ). Preliminary reports on DCVax-Brain clinical outcomes seem to follow these
trends. DCVax-Brain has been granted an Orphan Drug designation and received
clearance from the FDA to commence a phase II clinical trial for glioblastoma mul-
tiforme. DCVax-Lung has received clearance from the FDA for phase I trials.
Imetelstat (Geron Corporation’s GRNVAC1) is a therapeutic cancer vaccine com-
prised of autologous DCs loaded ex vivo with telomerase reverse transcriptase
(hTERT) mRNA. hTERT represents an attractive target for cancer immunotherapy
because it is overexpressed in most human tumors. Imetelstat is injected into intra-
dermally from where the dendritic cells travel to the lymph nodes and instruct cyto-
toxic T-cells to kill tumor cells that express telomerase on their surface. Results of
the fi rst completed phase I/II clinical trial of Imetelstat in metastatic prostate cancer
patients showed that the vaccine was well tolerated with no major treatment-related
toxicities (Su et al. 2005 ). In addition, telomerase specifi c T-cell responses were
generated in 19 of 20 subjects and vaccination was associated with a statistically
signifi cant increase in PSA doubling time and clearance of prostate cancer cells
from the patients’ blood, indicative of potential clinical response. Imetelstat is a
potent and specifi c telomerase inhibitor and so far the only drug of its class in clini-
cal trials (Röth et al. 2010 ).
Vaccines Based ON Genetically Modifi ed Dendritic Cells DCs, that have been
generated in vitro and transduced with genes coding for tumor-specifi c antigens or
pulsed with tumor specifi c antigen or peptide, could be useful for induction of cyto-
toxic T cell responses. Genetic engineering of DCs to express immunosuppressive
or immunoregulatory molecules may provide a novel method to promote graft toler-
ance, reducing dependence on systemic immunosuppression.
Gene therapy techniques can be applied to DC vaccines using recombinant non-
replicating viral vectors to provide effi cient and reliable means of gene transfer.
Genetic material is introduced into DCs to provide them a renewable source of
Personalized Cancer Vaccines