Biological Therapy for Cancer Treatment: Immunotherapy and Checkpoint Inhibitors

Running head: BIOLOGICAL THERAPY
Biological Therapy
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1BIOLOGICAL THERAPY
Biological therapy is a special type of treatment process in which a living organism is used to
treat a specific disease. Not only a living organism, but any substances derived from any
organism and any agent produced in a laboratory can also be used as a substance to treat a
disease (Priyadarshani, Li and Yao 2016). In recent time, the use of biological therapy has
become very common in the treatment of Cancer therapy. The biological therapies have
positively contributed to the advancement of the cancer therapies and often it is reported that, in
treatment ofadvanced-stage nonsmall cell lung cancer (NSCLC) the use of the biological
therapies has reduced the mortality rate in the world. Such biological therapies that are used for
the cancer treatment, are generally attacks the cancer cells by stimulating the immune system of
the body (Hersh 2016). In this biological therapy genotype is targetedwith druggable targets
with predefined clinical actionability and those genes, that are targeted, are HER2, RET, BRAF,
MET, NTRK1. These types of biological therapy used for the cancer, are referred to as
immunotherapy. However, this technique does not attack the cancer cells directly (McGranahan
and Swanton 2015). Therefore, there are several biological therapies, such as antibody therapies,
targeted therapies are associated with the direct interaction with the cancer cells. Immunotherapy
is one of the most common biological therapy that can be used for the treatment of cancer in a
wide manner. Therefore most of the biological therapy technique generally use the mechanism
of immune checkpoint inhibitor in the biological therapy of various cancer treatment. (Li et al.
2017). In this essay, the biological therapy, specifically the immunotherapy for cancer and use of
this therapy are highlighted in a brief manner.
Immunotherapy for the cancer treatment has various types such as immune checkpoint inhibitors,
adoptive cell transfer and non-specific immune stimulation. The use of the check point inhibitors
are used in a wide manner in recent times in the treatment of the cancer. The use of immune

2BIOLOGICAL THERAPY
system against the cancer cells in the body, influences the fate of development of the cancer cells
in the body and as a part of this, the agents also act as an extrinsic tumor suppressing agent that
are associated with the destruction of the tumors and restrict the development of the tumor cells.
It is observed that immune suppression can be mediated through the use of cytotoxic T-
lymphocyte associated antigen-4 (CTLA-4) and through Programmed death-1 (PD-1) (Sharma et
al. 2017). These two agents are used as an immunosuppressing agents as they are expressed on
the T cells. The immune checkpoint techniques can be used in various types of cancers such as
melanoma, renal cell carcinoma, non-small cell lung cancer. The immune therapy for the cancer
therapy mainly tries to give a safeguard to the immune system of the body. The T-cell therapy
and immune blockade checkpoints are mostly used immunotherapy for the treatment of cancer.
The blocking of negative immune regulators will help the human body to combat against the
cancer. As a part of the immune check point therapy, BCG is widely used as a treatment process
of cancer treatment (Nagarsheth, Wicha and Zou 2017). BCG was first approved by FDA as an
immunotherapy reagent and it is observed that in US the use of this therapy had lowered the risks
of Bladder cancer (BC) in the US by 70% approximately. There are various inhibitory immune
checkpoints such as APC cells, cancer cells and T cells. The T cell is activated when it makes
association with the Major histocompatibility complex (MHC) on the APCs or on the surface of
the tumor cells. Whenever, a T cell interacts with an antigen that is presented on the surface of
the cancer cell by the MHC class I molecules, the cancer cells shows cognate ligands to be
associated with the inhibitory checkpoints expressed on the surface of the T cell. Generally it can
be said that, the immune checkpoint proteins are located on the cell surfaces of the lymphocytes
which are specific for the tumor cells (Farkona, Diamandis and Blasutig 2016). In order to
inhibit the functions of cancer cells, the interaction property between the checkpoint ligands and

3BIOLOGICAL THERAPY
their ligands can be used and as result, the immune system will be engaged against the tumor
cells of the body. CLAT-4 can be used as am immune checkpoint blockers and it exerts its
inhibitory effects when it binds with the ligands named CD86 , CD 80 and they are quite similar
with the function of CD28. However, both the two agents have much higher affinity than that to
the CD28. This competitive bindings inhibits CD-28 induced activation of the T-cell. As a result,
the production rate of cytokine is also hampered. Not only the CTLA-4 but , the PD-1 can also
be used as a blocking agent of immune check points and it is also widely used in the treatment of
cancer therapy. The PD-1 is one of the activated protein that is expressed on the surface of the T
cell. The PD-1 generally can bind with the two types of receptor that are PDL1 and PDL2. The
PDL1 is highly expressed in the APCs, epithelial cells, T-lymphocytes and in the tumor cells
(Baumeister et al. 2016). The secretion of PDL1 from the overexpressing tumor cells protect the
tumor cells from the CD8+ mediated cell lysis. So it can be said that blocking of PDL1 will
inhibit the binding of the PD1 with its receptor and this will allow the T cells to destroy the
tumor cells. In a study it was noted that, use ofPidilizumab, a humanized monoclonal IgG4
antibody is capable of targeting the receptor of PD1, has become quite successful in the
treatment of advanced melanoma patients. In the phase I of this study, 37-38% of patients had
reported about positive outcome (Gotwals et al. 2017). In another study by Ohaegbulam et al.
(2015) , also showed the effectiveness of Pidilizumab in the blocking of PD1. In this, study, the
blocker is used in the treatment of various melanoma patients and it was observed that the
objective response rate was almost 66% among the study group of 32 patients and the patients
who were given in a rate of 10mg/kg ,showed the highest response.
Mechanism of CTLA-4 Mediated therapy