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4.2 Antibody based targeted therapy 77

methods can be effective in treating glioblastoma. The antibody they used in this
study is IIIA4, which is a EphA3 monoclonal antibody (mAb) [17].
Antibody based targeted therapy may be the most effective way to treat various
malignancies and cancers. But the basic point is that most of these antigens are not
expressed only in tumor cells, but also expressed in healthy cells! It is important
to state that today the problem with therapies for the treatment of cancer is not the
destruction of cancer cells, but the destruction of cancer stem cells, and due to the
heterogeneity of cancer stem cells, and since these cells express similar markers to
noncancer stem cells, it is not possible to detect these two cell types using a spe-
cific marker. And this makes it difficult to reach the goal of antibody based targeted
therapy (which eliminates tumor cells without affecting healthy cells). As an instance
CD105 is known as the proliferation marker for endothelial cells and it is overex-
pressed on tumor neo vasculature, but also expressed in normal cells.
In this regard, attention should be paid to the specific epitopes of the antigens that
can be different in tumor cells and normal cells or a more detailed and specialized
examination of which molecules are expressed in cancer cells at the cell surface,
while expressed in healthy cells.

4.2.2 Whole antibody or antibody fragments
Antibody fragments are small and simple structure that today is highly regarded
because of the many advantages they have over the use of whole antibodies. Antigen-
binding fragments (Fab) and single chain variable fragments (scFV) are common
antibody fragments that have been investigated and also another type known as “third
generation” (3G) molecules. The Fab fragments are consisting of one constant and
one inconstant domain of heavy and light chains, whereas in scFV fragments, the
varying areas of heavy and light chains are merged and the constant heavy and light
chain that was in the previous state is not here and in the case of the third type, it
consists of only one variable heavy chain (Fig. 4.3) [18,19].
As already mentioned whole antibodies are much more successful in treating
hematological malignancies than solid tumors, and this is due to the size of anti-
bodies (150 kDa) that are restricted to penetrate solid tumors. Lack of influence
of antibodies to solid tumors can be solved using smaller antibody fragments (it
is about 50 kDa for Fab and 25 kDa for scFV) [20]. Unlike whole antibodies, the
antibody fragments do not compete with endogenous immunoglobulins or does not
bind to FC receptors on healthy cells due to lack of FC portion and other benefits
of the absence of FC portion, is reducing the immunogenicity potential of anti-
body fragments based drugs. Another advantage would prefer antibody fragments
to whole antibodies is more sensitivity in antigen detection [21]. Considering the
advantages mentioned above for using antibody fragments instead of whole anti-
bodies, the attention of researchers has been drawn to the use of antibody frag-
ments in recent years. For example, in a study that was carried out in 2016 by
Mazzocco et al. anti-PSMA (prostate-specific membrane antigen) scFv fragment is
used to diagnose prostate cancer. They have labeled ScFvD2B that is an anti-PSMA