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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