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4.5 Antibody-drug conjugate 89

FIGURE 4.10 Antibody-drug conjugate.

mortality, so their production voluntarily stopped. Latest studies have revealed that a
lower dosage of this ADC could be beneficial in fighting against AML [55].
More recently, three ADC drug have been approved. These are T-DM1, brentuximab
vedotin, and inotuzumab ozogamycin, against CD22 which was approved in 2017 for
those who suffer from ALL (acute lymphoblastic leukemia) and phase I and phase II
clinical trials display promising results. Moreover, the combination of ADCs with other
common treatments such as chemotherapy would increase the success rate [58,60].
In order to determine the ADCs pros and cons, the basis function of ADCs must
be correctly understood. It would be worth mentioning that ADCs’ selective ability
leads to their movement into the tumor’s location. Secondly, ADC attaches to cells
that present antigen and are entered into endosomes/lysosomes. Finally, the toxic
drug is released and links to its final target which would be: DNA, tubulin causing
apoptosis. In some cases the toxic drug diffuses from dead cells, resulting in other
abnormal or normal neighbor cell apoptosis and this happens due to a membrane per-
meability [61] named Bystander killing. This process has been shown in Fig. 4.11.
In Fig. 4.11, a schematic illustration of ADCs function by encountering the tumor
cell is portrayed.
We can see the following:
a) ADCs movement to tumor environment
b) ADC binding to target antigen on the cell surface
c) Endocytosis of both antigen and ADC
d) Nonlysosomal drug released in cleavable payloads after ADC internalization