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antigen for presentation; this should lead to more sustained expression of antigen.
The expression of viral (and therefore foreign) genes may boost the immune
response, but this antiviral immunity primed by DCs may cause the immune system
to destroy DCs rapidly in subsequent rounds of immunization. One solution may be
to use viral vectors that do not result in the expression of viral genes, such as retro-
viruses or “gutless” adenoviral vectors. Adeno-associated viruses can be used to
transduce human DCs and their main advantage is a decrease in viral-derived epit-
opes leading to decreased immunogenicity of the vector.
Lentivirus vectors can be used for genetic modifi cation of human DCs and they
have an advantage over retroviral vectors that they do not require target replication
for effi cient transduction. Approaches facilitating generation of DC vaccines for
clinical trials and enhancing their viability, biodistribution, and capacity to stimu-
late antigen-specifi c immune responses are critical for immunotherapy. In one
study, mouse bone marrow cells were programmed with lentiviral vectors so that
they produced GM-CSF and IL-4 in an autonomous manner (Koya et al. 2007 ).
Mice vaccinated with genetically modifi ed DCs self-differentiated in vitro or in vivo
and produced potent antigen-specifi c responses against melanoma, which corre-
lated with protective and long-term therapeutic anticancer effects. Thus, DC precur-
sors can be genetically engineered after a single ex vivo manipulation, resulting in
DC vaccines with improved activity.
Fusion of Tumor Cells with Dendritic Cells to Produce Cancer Vaccines In this
approach, a product is created using a technique that fuses the patient’s own tumor
cells with powerful, immune-stimulating DCs. The fusion product is then injected
back into the patient with the goal of sparking a specifi c immune response against
the cancer. This individualized cell therapy presents the full complement of antigens
specifi c to the patient’s tumor.
The BIOVAXID™ (Accentia BioPharmaceuticals) cancer vaccine evokes the
power of each patient’s immune system and primes it to recognize and eliminate
malignant lymphoma cells, while sparing normal B cells. In this individualized
therapy, cells are harvested from a patient’s lymph node, and the unique cancer
biomarkers on the outside of their cancer cells are identifi ed. To create this idiotype
vaccine, the antigen-bearing tumor cells are fused to antibody-producing mouse
cells that act as mini-factories, churning out large quantities of the protein antigens,
which are then given back to patients with an immune system booster. By priming
the immune system with this antigen in the form of an autologous vaccine, the vac-
cine induces an immune response against the cancerous cells and creates an immune
memory. Because it is derived from individual patient’s cancer cells, the vaccine is
a true targeted, personalized therapy. The vaccine’s anticancer effect is different
than non-targeted traditional therapy, as it arises from the immune system’s defense
cells’ innate ability to selectively target foreign antigens. Moreover, the immune
response triggered by the vaccine against the cancerous tissue is a natural disease-
fi ghting mechanism and is associated with minimal toxicity. Phase I and II clinical
trials demonstrated the immunogenicity, safety and therapeutic effi cacy of BiovaxID
(Reinis 2008 ). It is in phase III clinical trials at M. D. Anderson Cancer Center
(Houston, TX) for follicular lymphoma.
10 Personalized Therapy of Cancer