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74 CHAPTER 4 Immunotherapy
4.1.4 Tumor infiltrating lymphocyte
TIL therapy utilizes the patient’s T cells which are gathered from a section of surgi-
cally removed tumors. Although these cells may detect the cancer, few of them are
usable. The number of these cells is proliferated and treated (with the aim of active
the lymphocytes) in the lab and then returned to the patient’s body to help their
immune system eradicate cancer cells.
Melanoma, among tumors with infiltrating lymphocytes, is one of the first exam-
ples where tumor reactive T cells could be increased in vitro to a large population
for adoptive transfer. For nonmelanoma tumors, the use of novel methods such as in
vitro activation of costimulatory ligands, or selection of PD1+ tumor reactive TIL
has shown efficient preclinical results for ovarian, breast, and colorectal cancers.
In addition to the benefits, this method also handles limitations such as toxic-
ity due to intense preinfusion and postinfusion regimens, and inappropriate patient
selection that limits the use of this approach [7].
4.2 Antibody based targeted therapy
Antibody based targeted therapy as a method for treating cancer has been invented
since 40 years ago and is now one of the most important and successful ways to treat
patients with hematological malignancies and solid tumors. The basis of this method
refers to observation of expression of antigens by tumor cells using serological tech-
niques in 1960 [10]. Subsequently, in 1975, the production of monoclonal antibod-
ies was developed using the hybridoma technology by Milstein and Köhler [11].
Identification and production and use of antibodies was continued until 1997 when
rituximab was introduced as the first full length chimeric antibody and used to treat
Patients with Relapsed low-grade non-Hodgkin’s lymphoma [12]. Following this,
scientists were drawn to the use of antibodies and antibody based targeted therapy
as a solution to treat malignancy. So today, antibody based targeted therapy, that is,
the use of whole antibody or specific antibody fragments; alone or in combination
with drugs, toxins, radionuclides, etc. is very common and used in clinical practice.
In order to better understand the function of antibodies to treat malignancy, there
is a need to briefly define malignancy. There are several basic question in this regard:
What is cancer? What is the difference between benign tumor and malignant tumor?
What is the meaning of metastasis? In simple terms, normal cells grow and divide
slowly and there are some components in the cell’s structure that control them. Can-
cer occurs when the cells change, quickly grow and divide without any control. When
the tumor is formed, if it continues to grow unbroken and invades the surrounding
tissue, called a malignant tumor; a malignant tumor can enter the blood vessels or
lymph nodes and go to other parts of the patient’s body, where it begins to grow and
divide and create a new tumor. This cancer spread in the body is called metastasis.
One of the most important goals for cancer treatments is to prevent malignant
activity of the cancer cells without affecting the activity of healthy cells. And
because one of the important features of the method of antibody based targeted