Page 125 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

5.2 Innate cell-based therapy 123

a large number of activating an inhibitory receptor, and whether or not NK cells are
activated depends on the response of all these receptors, some studies show that some
tumoral cells alter their expression of MHC class I molecules.
NK cells in cancer immunotherapy have received much attention because they are
widely cytotoxic and require a short time to lyse tumor cells and most importantly, NK
cells that enter the patient's body in NK cell therapy do not need to strict HLA match-
ing and also in NK cell therapy there is no possibility of graft-versus-host disease.
And numerous clinical studies have shown that the use of allogeneic NK cells against
various types of hematologic malignancies or solid tumors can be safe and effective.
Due to the advantages of using CAR-T cells and the success of these types of
cells against neoplasms, which have been discussed in this chapter, researchers have
moved toward the production of CAR-NK cells in order to increase the ability to kill
the tumors in them. CAR-NK cell therapy has two major advantages over CAR-T
cell therapy. First, the CAR-NK cells through their receptors can identify the tar-
get tumor cells, and unlike the CAR-T cell therapy that the tumor cells can escape
through downregulating the CAR target antigen, in NK cell therapy, the tumor cells
can rarely escape. Second, on the other hand, NK cells that enter the patient's body in
NK cell therapy do not face immune rejection by the host [27].

5.2.4 Innate or adaptive immunity?
Recent researches have shown that NK cells have both innate and adaptive immune
system properties. NK cells in the face of the tumors either kill them independently
or cause T cells to be active and also in some cases, NK cells use both of these meth-
ods to eliminate tumor cells. According to investigations done to evaluate the efficacy
of NK cell therapy as compared to the use of adaptive immune system cells against
cancer, the results have indicated that although it has been reported in some cases
that the process of purifying and uniformly dispersing of NK cells has been difficult,
but in most cases and especially in recent years due to the same effectiveness of NK
cells and the adaptive immune system cells, NK cell therapy has been preferred to
other similar methods [28]. For example, in a study conducted in 2018, researches
have compared the antitumor effects of iPSC-NK cells and CAR-T cells in an animal
model of mice. The results of this study have shown that although the antitumor
effects of both methods were almost identical, the mice that treated with NK-CAR-
iPSC-NK cells had significantly longer survival and did not experience weight loss
and other side effects such as increased levels of cytokines, unlike CAR-T cell ther-
apy [29]. Other studies in recent years, in particular in 2018 and 2019, have indicated
that researches in the field of cancer immunotherapy have switched to NK cell ther-
apy because of the availability and lower cost of NK cell therapy than T cell therapy.

5.2.5 Preclinical and clinical examination of innate cell therapy
As noted in previous sections, despite all advantages of methods such as vaccina-
tion and targeting tumor cells through antibody-antigen binding which have been