Page 93 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

4.5 Antibody-drug conjugate 91

neighboring cell’s death as well as systemic toxicity as a result of the bystander
effect. This is to say that the part of membrane which is free of tumor antigens
lead to the spreading of drugs after internalization. Moreover, the rate of
expression must be more than normal tissues.
2) The manufactured antibody must be able to become internalized into the cell
by cell receptors and after ADCs administration, the tumor antigen down
regulation must not occur.
3) An optimal ADC should have a minimum release of the cytotoxic drug before
reaching to the target cell for reducing the adverse effect [60].
One of the most vital issues in cancer treatment is the ability to target tumor-
initiating cells (TICs), which are cancer stem cells. These cells are the main factors
responsible for the growth of tumors, metastasis, etc., therefore targeting TICs is
crucial, hence why we will discuss this further.
4.5.1.1 Specific antigens in cancer stem cells
In 1994, scientists found that only a rare amount of cancer cells have the features of
malignancy and can be metastatic. These cells are named cancer stem cells [65]. It is
hypothesized that cancer stem cells can survive from common treatments like che-
motherapy and also have self-renewal abilities [64,66], so from the aforementioned
data, we can conclude that targeting cancer stem cell antigens may lead to patient
treatment. Although it has appeared that some molecules that are expressed on the
membrane of TICs like CD47, CD44, CD133, CD33, etc., these markers are mostly
expressed in both cancer stem cells and healthy stem cells. Therefore some of which
that display a higher expression rate in tumor stem cells are considered for ADCs
usage [66]. Although a vast majority of scientists are in agreement with the cancer
stem cell theory and attempts in dealing with these cells were continued, nobody has
been successful in this regard, so investigating the possible reasons in these preced-
ing failures is essential:

1) The initial theories on cancer stem cells considered the number of these cells at about
one in a million but it has been shown that the number of these cells may differ from
case to case, and could reach the number of one stem cell per four cancer cell.
2) As cancer stem cell markers are not specific, or unique, and as there are no
series of markers to use to identify and isolate cancer stem cells, scientists could
not purify CSCs in order to study their properties.
3) The problem with cancer stem cell plasticity is really important. That is to say
that differentiated tumor cells could become cancer stem cells to compensate
the loss of cancer stem cells, therefore it is vital to eradicate all tumor cells not
just CSCs [65].

4.5.2 Antibodies
Antibody is a protein that is shaped like a “Y,” and it is produced in blood by B
cells when the immune system becomes activated. It is the ability of antibodies in