**Following are the types of Monoclonal antibodies:**

#### 1.**Naked monoclonal antibodies**


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overall survival [12].

*Therapeutic Applications of Monoclonal Antibodies in Urologic-Oncology Management…*

thereby causes the inactivation of the protein by blocking it [7].

c.E.g., trastuzumab is a monoclonal antibody that acts against the HER2 protein and used in the treatment of carcinoma of the breast in which this protein is expressed in larger amounts on the surface of the cancer cells. It

As the name suggests these are in combination with the chemotherapy drugs or radioactive materials. These are referred to as tagged or labeled mAbs. They directly deliver the therapy to the target cells causing minimal damage to the normal cells surrounding them after precisely identifying them [8]. It then delivers the toxic substance where it is needed most. They can be of the

a.**Radiolabeled antibodies:** These are conjugated with radiolabeled particles. An excellent example is Ibritumomab tiuxetan which works against the CD20 antigen found on B lymphocyte cells. It is made up of radioactive substance (Yttrium-90). The mAb works on the target cancer cells and then the radioactive materials target the destined cells and also the nearby cell. *Radioimmunotherapy* (RIT) is the name used for this type of treatment [9].

b.**Chemolabeled antibodies:** These mAbs have chemotherapy drugs attached to them. Eg: Ado-trastuzumab emtansine, an antibody that targets the HER2 protein (breast cancer). It is covalently linked to the cytotoxic agent DM1

These can attach to 2 different types of antigens at the same time, these have also been explored in cancer therapy and drug delivery. Example is blinatumomab, used in the treatment of acute lymphoblastic leukemia. It works by directing the body's T-cells (part of the immune system) to target and bind

Prostate cancer is one of the most common cancers with its incidence being high

with the CD19 protein on the surface of B-cell lymphoma cells [10].

in Americans but lesser in the Asian population. It develops within the prostate gland that is responsible for the production of seminal fluid. Cancer therapy considered for prostate cancer includes radical prostatectomy, radiation therapy, chemotherapy, brachytherapy and hormone therapy [11]. The role of mAbs in Prostate cancer treatment has not been very successful. Several trials have been carried out

Ipilimumab was the first immune checkpoint inhibitor which received FDA approval for the treatment of metastatic melanoma. It worked as the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This stimulated its exploration for the treatment of prostate cancer. Use of this mAb in conjugation with radiation therapy did show antitumor activity in the form of decreasing PSA levels. This was a phase 1 trial. Hence, phase 3 clinical trials were conducted for further evaluation where subjects were randomized to ipilimumab after chemotherapy or radiation therapy. These trials did show progression free survival but missed its endpoint of

Clinical trials on another mAb Nivolumab remains under investigation. In a first of its kind combination immunotherapy using monoclonal antibodies, Ipilimumab

to check for its efficacy, the details of which have been mentioned below.

*DOI: http://dx.doi.org/10.5772/intechopen.96911*

2.**Conjugated monoclonal antibodies**

3.**Bispecific monoclonal antibodies**

**3. Monoclonal antibodies and prostate cancer**

following types;

*Therapeutic Applications of Monoclonal Antibodies in Urologic-Oncology Management… DOI: http://dx.doi.org/10.5772/intechopen.96911*

c.E.g., trastuzumab is a monoclonal antibody that acts against the HER2 protein and used in the treatment of carcinoma of the breast in which this protein is expressed in larger amounts on the surface of the cancer cells. It thereby causes the inactivation of the protein by blocking it [7].

#### 2.**Conjugated monoclonal antibodies**

*Monoclonal Antibodies*

**1. Introduction**

Modern advances and a quantum leap in the field of cancer therapy has been promising to oncologists with new tools to fight many cancers. The immune system has multifunctional units referred to as antibodies, mostly polyclonal which facilitate humoral and cellular reactions to antigens [1]. However, it is possible to produce large quantities of an antibody from a single B-cell clone which are called as *Monoclonal Antibodies (MAbs).* Using these antibodies for therapeutic purposes is termed as Immunotherapy. Immunotherapy in recent times has been propitious across a number of cancer types. Stimulating results with MAbs directed towards both established and emerging targets indicate its potential key role as a therapeutic agent [2]. These are being tested in earlyand late-stage clinical trials. In the last 35 years over 100 Monoclonal Antibodies have been considered potential as drugs and many have been approved. The usage of the monoclonal antibodies in cancer therapy requires the understanding of the biological role of various antigens involved in tumor growth [3]. In cancer patients' immunity system is often altered. The purpose of immunotherapy with monoclonal antibodies is to interfere with synergic activity of immunosuppressive environment created by T cells, cytokines, interleukins and tumor growth factor [4]. In many cancer treatments, the monoclonal antibodies have been robust enough, however in some, combinatorial treatments including monoclonal antibodies, chemotherapy and vaccines have been successful thereby bringing together cancer immunologists and clinicians required for the management of cancer in the near future [5]. This chapter will focus on Immunotherapy using Monoclonal antibodies for many urologic oncology types such as prostate, renal, bladder, testicular and penile with a hope to highlight its clinical

utility and also its mechanisms of action in each of these cancer types.

**2. Types of monoclonal antibodies and their mode of action**

• Murine: These are derived from mouse. Called as 'omabs'

**Following are the types of Monoclonal antibodies:**

Called as 'zumabs'

mouse. Called as'ximabs'

leukemia (CLL).

1.**Naked monoclonal antibodies**

**There are several ways by which the mAbs are made. They are as follows:**

• Human: Theses are derived from the human source. Called as 'umabs'

• Humanized: Here the mouse proteins are attached to the human protein.

• Chimeric: variable regions are from humans and constant regions are from

a.These are the most common types of antibodies which are not attached to the radioactive material or any chemotherapy drugs. They act independently and have been extensively used to treat cancer. They attach themselves to antigens on cancer cells, or even non cancerous cells and other free-floating

b.E.g., alemtuzumab. This is used in the treatment of multiple sclerosis and

proteins. They can also act as immune checkpoint inhibitors [6]

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As the name suggests these are in combination with the chemotherapy drugs or radioactive materials. These are referred to as tagged or labeled mAbs. They directly deliver the therapy to the target cells causing minimal damage to the normal cells surrounding them after precisely identifying them [8]. It then delivers the toxic substance where it is needed most. They can be of the following types;


#### 3.**Bispecific monoclonal antibodies**

These can attach to 2 different types of antigens at the same time, these have also been explored in cancer therapy and drug delivery. Example is blinatumomab, used in the treatment of acute lymphoblastic leukemia. It works by directing the body's T-cells (part of the immune system) to target and bind with the CD19 protein on the surface of B-cell lymphoma cells [10].

#### **3. Monoclonal antibodies and prostate cancer**

Prostate cancer is one of the most common cancers with its incidence being high in Americans but lesser in the Asian population. It develops within the prostate gland that is responsible for the production of seminal fluid. Cancer therapy considered for prostate cancer includes radical prostatectomy, radiation therapy, chemotherapy, brachytherapy and hormone therapy [11]. The role of mAbs in Prostate cancer treatment has not been very successful. Several trials have been carried out to check for its efficacy, the details of which have been mentioned below.

Ipilimumab was the first immune checkpoint inhibitor which received FDA approval for the treatment of metastatic melanoma. It worked as the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This stimulated its exploration for the treatment of prostate cancer. Use of this mAb in conjugation with radiation therapy did show antitumor activity in the form of decreasing PSA levels. This was a phase 1 trial. Hence, phase 3 clinical trials were conducted for further evaluation where subjects were randomized to ipilimumab after chemotherapy or radiation therapy. These trials did show progression free survival but missed its endpoint of overall survival [12].

Clinical trials on another mAb Nivolumab remains under investigation. In a first of its kind combination immunotherapy using monoclonal antibodies, Ipilimumab

plus nivolumab has been gaining responses as being reported in a phase 2 trial on metastatic castration resistant prostate cancer. Pembrolizumab is also an immune checkpoint inhibitor [13]. It has received approval from FDA for the treatment of prostate cancer. In these solid tumors, microsatellite instability (MSI) and mutations in mismatch repair genes (MMR) has been observed. Pembrolizumab is evaluated for in a patient after other effective treatments (such as sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223, etc.) has been ruled out [14]. Combination therapies either with multiple immunotherapies or with immunotherapy and chemotherapy/RT, are currently being evaluated in prostate cancer. The optimal timing of immunotherapy in prostate cancer also remains unclear. Although much work remains to be done, the promise of prostate cancer immunotherapy remains unclear. There have been modern advances in the treatment of prostate cancer, however there is no curative treatment option once prostate becomes metastatic.
