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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
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