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4.7 Nonspecific immunotherapy 103

In a clinical trial phase1/1b study the OTSGC-A24 cancer vaccine was used in 24
patients with gastric cancer for 4 weeks in order to evaluate the safety and immune
response on the basis of induction of CTL. The results have demonstrated the safety
of the vaccine and 15 patients showed positive CTL after 4 weeks [99].

4.6.7 Future prospect
It would be clear that combination of cancer vaccine therapy with other methods
including: radiotherapy and chemotherapy boost the results, so this vital issue is of
great concern. Moreover, one of the most important complications in cancer treat-
ment is the vitality of cancer stem cells, hence developing vaccines with the abil-
ity of stem cell recognition and killing is demanding. Furthermore, there are some
well-known stem cell markers such as Vimentin [100], it is important to understand
whether they express on the surface of the cell or inside the cells in tumor cells,
whenever we find the markers location, we can better manage our vaccines. As a last
point it is worth mentioning that, although newly manufactured vaccines are focused
on personalized vaccination, finding global and general methods for cancer vaccina-
tion with the usage of multiple fragments would be demanding.

4.7 Nonspecific immunotherapy

In general, the goal of all cancer therapeutic is the eradication of cancer cell colony
and to prevent metastasis [101]. However, nonspecific Immunotherapy has focused
less on identification and destruction of the malignant cell, so it has more attention
on inducing widespread changes between immune system and cancer cells in order
to make a modulation on this battle. These therapies are less sensitive to antigen-spe-
cific therapies. It is also known as immunomodulatory therapies [100,101]. Although
it mostly has used as an adjuvant (along with the main treatment) to improve the
immune system, another type of immunotherapy like a vaccine, however, some
nonspecific immunotherapies have given themselves as a cancer treatment. These
therapies can include cytokines and chemicals released by immune system cells such
as interleukins and interferons which are essential for growth and controlling the
immune system cells and blood cells. Usage of drugs like immune inhibitor check-
points which are similar with cytokines can boost the immune system, but unlike
cytokines, these are not naturally found in the body so they are injected to the body
like a drug [101-103].
Nonspecific immunotherapy has different mechanisms that can be categorized
into direct antitumor effects, activation of innate immunity, a reversal of immune
suppression and antigen-nonspecific T-cell activation. And they likely include
macrophages, non-MHC-restricted killing by NK cells and memory T cells. They
are varied to each other and some of them are too complex which have not been
understood until recent years. Fig. 4.14 clearly shows the mechanism of nonspecific
immune therapy via specific immune therapy [101].