Page 74 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

72 CHAPTER 4 Immunotherapy

can be modulated by cytokines such as IFN-γ and TNF-α, which helps retain the
peripheral tolerance. The detailed mechanism of the inhibition of PD-L1 and PD-L2
in T cell activity is yet to be clarified. It may involve the enhanced programmed cell
death caused by the binding of PD-1 to PD-L1.

4.1.2 Oncolytic viral therapy
Oncolytic viral therapy (OVT) is a new approach for cancer treatment that has
potential. Oncolytic viruses (OVs) can duplicate in tumor cells but not in healthy
cells, by lysis of the tumor mass. Some viruses have the tendency to infect and kill
tumor cells, known as OV, and this category includes viruses available in nature as
well as manipulated viruses in the lab to efficiently replicate in tumor cells without
damaging normal cells. The use of OVT has long been viewed as an appropriate
approach for directly killing cancer cells. The aim of OVT is not only to kill cancer
cells but to also activate the immune system that is suppressed by the tumor microen-
vironment. The biological mechanisms used by viruses to eradicate tumors depend
on different factors such as the virus, the target tissue or cell, and the biological
pathways targeted. OVT are capable of making long-term memory. Transformed
cells can evade from the immune system by transforming their antigens and becom-
ing undetectable to leukocytes in a process named “immunoediting.” When OVs
infect cancer cells, an inflammatory response is induced. These viruses are able to
stimulate immunogenic cell death (ICD) and this form of apoptosis can stimulate
an efficient antitumor by activation of dendritic cells (DCs) and the stimulation of
specific T lymphocytes.
The first FDA approved OVT was a treatment for a melanoma known as talimo-
gene laherparepvec. This is a modified herpes simplex virus (HSV) that enhances the
number of tumor-specific CD8+ T cells and decreases the number of regulatory and
suppressor T cells.
Ultimately, there are obstacles that come with the use of this approach. The main
obstacle is the host immune response to a viral infection (especially in IV administra-
tion) after IV injection, the virus is phagocytized and cannot reach the tumor site. To
overcome this problem, accurate design of the optimal viral gene edition and attach-
ment of combinations is needed [6].

4.1.3 Adoptive cell therapy
For the treatment of less immunogenic tumors, such as pancreatic cancer and MSS
(microsatellite stable) colorectal cancer, the use of immune checkpoint inhibitors
(ICIs) alone is not enough. Consequently, collecting a population of tumor-reactive
T cells through adoptive cell therapy (ACT) would make immune-based therapies
possible [7]. ACT is a cancer therapy strategy that uses either natural host cells that
show antitumor reactivity, or host cells that have been genetically engineered with
antitumor TCRs or chimeric antigen receptors (CARs). ACT has numerous benefits
compared to other types of cancer immunotherapies, depends on the active in vivo