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126    CHAPTER 5  Cell therapy




                            Self-renewal and differentiation abilities that progenitor cells have cause to use
                         them in repairing the tissue after chemotherapy. Clinically it has been shown that
                         transplantation of hematopoietic stem cells, will ease the lifelong hematological
                         recovery after treatment with high dose radiotherapy or chemotherapy. These cells
                         are collected from a donor and then injected to the patients with the goal to recon-
                         stitute bone marrow and to treat blood cells [39,40]. The collection of hematopoietic
                                                                         +
                         progenitor cells is different in some patients such as CD34  cells they collect with
                         T cells and in others they have been collected from an allogenic donor. And each of
                         them has a different method of collection [40].
                            The usage of progenitor cells in immune cancer therapy with the investigations of
                         the TCR and CAR has been increased [41]. There are three reasons why progenitor
                         cells are attractive to be used in TCR and CARs. First of all, HSCs have the ability
                         of long-term blood cell production hence, HSCs can produce effective T cells engi-
                         neered against the antigen of interest. They supply of T-lymphocyte progenitor cells
                         that can increase the potential for the development of immunological memory. These
                         cells are in contrast to the mature T cells that massively expanded before infusion.
                         Second, one problem of TCR mechanism as it said before was the toxicity that it can
                         provide due to targeting the normal cells. HSC can eliminate this target cytotoxic-
                         ity because they are not arranged yet in their germ line. So it can provide a specific
                         antigen for targeting. And the third one is the ability of HSC to mandate after high
                         dosing of conditioning regimens to increase clinical efficacy. This feature can help to
                         use HSC grafts as a way for Immunotherapy [41].


                         5.3.2  IPSC in cancer therapy
                         Induced pluripotent stem cells (iPSCs) are cells that have been derived from different
                         sources such as skin or blood cells that have the ability to reprogram back to the first
                         stage, for instance, embryonic progenitor stem cells [42]. This technique has widely
                         been used in regenerative medicine. But still it has several problems that need to be
                         solved. One of its problems is that it does not have the ability of robust differentiation
                         protocol toward a specific tissue with the generation of the cells.
                            Another field where these cells are used is in cancer. The first study in cancer was
                         on hematopoietic malignancy and then with the development of the novel model of
                         myeloid proliferation. It has progressed rapidly and has been used in different cancer
                         and more recently it is used in solid tumors and hereditary cancers [43].
                            As it was said earlier, the main goal of cancer immunotherapy is to stimulate
                         a steady immune response against the tumor cells. The immunological checkpoint
                         blockade is one of the new techniques that are used today as a new way in cancer
                         immunotherapy [44]. The main purpose of them is to enhancing the tumor-specific
                         activity of the immune system. To reach this goal, the immunoglobulins are the key
                         points and cell receptors such as CTLA4 is working as activators or inhibitors to ini-
                         tiate an immune inhibitory signal in the targeted tumor cells. This technique is used
                         as one of the cancer-immune methods but it has a problem in culturing and manipu-
                         lating immune cells ex vivo hence what has recently been used are embryonic stem
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