Page 102 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

100 CHAPTER 4 Immunotherapy

4.6.3 Tumor cell vaccines
In this method the TAAs of tumor cells are used for vaccination, these tumors could
be autologous or allogenic. These tumors should become inactive before vaccina-
tion because live tumors may express immune-suppressive cytokines and also they
are capable of producing new tumors in body. There are some methods to kill tumor
cells, one of the most common strategies is the freeze-thaw method. By repetition
of freeze and thaw process the tumor cell necrosis will happen and the cellular com-
partments including TAAs is released. Finally, TAAs are separated by centrifugation.
Another used strategy is promoting tumor death by irradiation which causes tumor
apoptosis and is milder than freeze-thaw method. Afterwards, the obtained TAAs
must be loaded in biomaterial platforms which are discussed further.
The benefit of tumor cells as a source of antigens is the ability of tumor vaccines
to produce strong immune response due to high amount of mutated antigens exist-
ing on cancer cells. Moreover, in the case of autologous tumor usage, the antigens
become more personalized boosting the immune responses. However, some disad-
vantages of tumor vaccines is their high rate of cost and it cannot be administered to
everyone in autologous tumor vaccines and low efficiency due to unspecific antigens
in allogenic vaccines [70].
Novel approaches in tumor cell vaccination have revealed the advantages of using
tumor cell lysate along with DCs. Different strategy on tumor cell lysate have newly
explored, like vaccines with three-dimensional polymer matrices in combination
with tumor lysates along with adjuvants and the efficiency of the system is proved in
models of murine with melanoma [93].

4.6.4 Viral vaccines
In 1890s the usage of bacteria in cancer treatment has figured out. Coley accidentally
has found that a patient suffering Sarcoma was getting better with erysipelas. These
results caused him to try treatments with inoculation of Streptococcus and Bacillus
prodigious. Thereby, he has declared that it was hard to induce meaningful infection
with the usage of inoculation strategy. Since then, researchers have tested divergent
bacteria including: Listeria monocytogenes (Lm), Clostridium novyi, and Salmonella
typhimurium. Some of these organisms have been used as pure vectors and some of
them in combination with adjuvant or DCs to express tumor antigens [89].
Viruses are other efficient organisms in cancer treatment. The usage of viruses is
not limited to attenuated viruses in combating viral diseases by induction of protec-
tive immunity. With the help of genetic advances, viruses have used as vectors to
express and deliver antigens in order to induce immune reaction, and this immune
reaction is not only usable in viral disease, but also in cancerous cells which are not
naturally immunogenic [89].
Recent attentions in utilizing viruses is not only limited to their usage as gene vec-
tors, but as direct toxic candidates to tumor cells, these viruses are called OVs [94].
OVs are viruses that have the ability to infect and kill tumor cells [95]. Recent
developments in the usage of these OVs have resulted in a huge realm of engineered