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124    CHAPTER 5  Cell therapy




                         occurred by adaptive immune system cells, in recent years, preclinical and clinical
                         examinations in the field of innate cell-based therapy has expanded dramatically. For
                         instance, Xiaowen Tang et al. in a clinical study in 2018 have examined the safety of
                         CD33-CAR NK cells in patients with acute myeloid leukemia (AML). In this phase
                         I trial study, which has included three patients with advanced AML, each patient has
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                         received 5 × 10  CAR NK-92 cells. The results of this study have shown that no
                         harmful effects were observed and the cost of using these cells was much lower than
                         the use of CAR-T cells [30].
                            In another clinical study conducted in 2016, the researchers have investigated the
                         effects of Healthy Donor-Derived Allogeneic NK cells in 17 patients with malignant
                         lymphoma or with advanced solid tumors. In this study, each patient has received
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                         a maximum of 3 × 10  highly activated NK cells (MG4101) and the results have
                         shown that this treatment was not only safe and effective but also effective in main-
                         taining the effector arm of patient's immune system response against cancer [31].
                            In another study in 2019, the safety and efficacy of allogeneic NK cells injec-
                         tion in patients with hepatocellular carcinoma have been investigated. In this clini-
                         cal experiment, 21 patients with primary hepatocellular carcinoma were enrolled.
                         Allogeneic NK cells were donated by relatives of each patient and the follow-up
                         time for patients was one year after NK cell therapy. The authors have reported that
                         after NK cells infusion, 10 patients had a fever, one had a partial headache, and
                         one patient had partial hepatalgia. And no other harmful event like graft-versus-host
                         disease (GVHD) happened. And the overall results of this study have indicated that
                         allogeneic NK cells are safe and effective in the treatment of primary hepatocellular
                         carcinoma and also the antitumor properties of NK cells play an important role in
                         activating the host's natural immune system and preventing the progression of the
                         disease [32].
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                            And in a preclinical study performed in 2017, about 5 × 10  human NK cells
                         (NK-92MI) were injected twice into an animal model of mice that had pulmonary
                         metastasis of anaplastic thyroid cancer (ATC). The results of these experiments have
                         shown that NK cell therapy can be effective in targeting and treating anaplastic thy-
                         roid cancer (ATC) and prevent metastasis to other sites [33].



                         5.3  Progenitor stem cell therapy
                         Stem cells are kind of cells that have the ability of self-renewal and to the production
                         of mature cells through differentiation [34]. Stem cells basically have categorized as
                         ‘embryonic’ (ESCs) or ‘somatic’ (SSCs). Somatic stem cells that also known as adult
                         stem cells are multipotent and can differentiate to any cell type. These are including
                         neural stem cells, mesenchymal stem cells, hematopoietic stem cells, and endothelial
                         progenitor cells. Investigation of functions and features of stem cells have opened a
                         new sight into the therapeutic methods for different diseases in particular in cancer
                         therapy [34,35]. Stem cells have the ability to migrate to solid tumors and micro-
                         metastatic lesions. This feature makes the stem cells as a specific antitumor agent.
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