Page 96 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

94 CHAPTER 4 Immunotherapy

4.5.5 Case study
In a study, Connors et al. have used brentuximab vedotin, which targets CD30, along
with chemotherapy for those who suffer from Stage III or IV Hodgkin’s Lymphoma.
The results have revealed that the overall rate of death and cancer progression was
4.9% lower for patients who were treated with the combination of chemotherapy
and ADCs, compared to those who treated with chemotherapy alone [68]. In another
investigation in 2018, phase I clinical trial on the efficiency of vadastuximab talirine
(which is an antibody) drug conjugate as single agent in AML patient with CD33-
positive was tested. The results have illustrated the safety and activity of vadastux-
imab talirine as monotherapy, and it is worth noting that the recommended dosage
for this drug is 40 µg/kg [69].

4.5.6 Prospect
As discussed, the knowledge of ADCs manufacturing has been greatly developed
in the past few decades and there are approximately 60 ADCs in clinical phase for
both hematological and solid tumors, and the approval of three ADCs raise the hope
of progressive usage of ADCs as novel cancer treatment methods in the near future.
Some key factors in developing new ADCs include:
1. A growing demand in recognizing cancer-specific antigens
2. Producing ADCs which are stable in the circulation system and are less
immunogenic
3. Inventing better payloads and methods to deliver more drugs into the target cells
4. Novel approaches in linkers and conjugation chemistries.

It is paramount to recall some problems scientists have faced in ADCs designing,
such as: the expression of target antigens in normal cells, heterogeneity of both tumor
cells and ADCs, low amount of payloads reaching the target antigen, instability of
linkers causing systemic toxicity, survival of cancer stem cells—leading to relapse, etc.
Novel methods have solved many of the aforementioned obstacles. For example,
site-specific conjugation resulting in near homogenous ADCs which increase the DAR
and therapeutic windows, humanized antibodies in decreasing the immunogenicity to
some extent, multiepitope targeting that helps scientists generalize ADCs to the vast
majority of people, usage of antibody fragments instead of whole antibody to improve
the ADCs penetration and finally, combination therapy which is of a great impor-
tance. The combination of chemotherapy along with ADCs would be recommended.

4.6 Cancer vaccine
The earliest indications of vaccines against tumors came into existence only after
the invention of tumor-specific antigens (TSAs) in 1967, which were pioneered by
George Klein. However, problems such as, low immunogenicity, toxicity and target-
ing issues was existed [70]. During the last decade, cancer therapies have significantly