Immunotherapy

immunotherapy

 

 

If you have someone around you who has cancer, you may have heard of a treatment called immunotherapy. This method uses the components of the patient's immune system to help him or her fighting cancer.  When cells start developing cancer, the immune system is intelligently stimulated to selectively attack these cancer cells. In this regards, the immune system will produce number of proteins in patient's body to fight cancer cells. Biological therapy or biotherapy are the new methods of immunotherapy which will be discuss later. What you will read next:

 

immunotherapy

How does the immune system work?

Immune system, cancer and the immunotherapy

Artificial cancer immunotherapy

Monoclonal antibodies

Types of monoclonal antibodies

monoclonal antibodies side effects

Vaccines

Preventive vaccines

Vaccines used to treat cancer

 

 

 

What does the immune system do?

A set of organs and their cells, together with the materials they produce, are responsible for keeping all parts of our body healthy against any external and internal harmful diseases, like bacterias and viruses. These organs and cells are collectively called the immune system.

This highly specialized and complex system is responsible for fighting against infectious agents such as viruses, bacteria, fungi and environmental toxins and preventing the body's cells from becoming cancerous. The function of this system is such effective that any unknown protein in the body, including components of viruses, bacteria or substances made by cancerous tumors, is identified and destroyed by this immune system as an unknown agent.

 

Why does the immune system fail to treat cancer?  

Unfortunately, in some occasions, the immune system fails to fight cancer cells because not every cancer cell is necessarily considered unknown by our immune system and sometimes the function of the immune system alone is not enough to fight and destroy cancer cells.

To make things worse, sometimes some cancerous tumors make substances that prevent the immune system from responding. To improve the immune system's ability to recognize and fight cancerous tumors and boost or improve its functionality, doctors and researchers use methods called immunotherapy.

 

Artificial cancer immunotherapy

  • Checkpoint Inhibitors
  • Chimeric antigen receptors CAR T-cell therapy
  • Monoclonal antibodies
  • Vaccines
  • Cytokines
  • Interferons
  • Interleukins
  • Immunomodulators
  • BCG bacteria
  • Imiquimod
 

Checkpoint Inhibitors:

These drugs prevent the immune system from stopping, and as a result, the patient's immune system becomes stronger and faster defending the body. The effectiveness of our immune system depends on how well it can identify cancer cells. However, the white blood cells fighting cancers may avoid attaching cancer cells if some proteins exist on their and cancer cell surface. The most important safety system checkpoints are:

  • PD1 inhibitors
  • PDL1 inhibitors
  • CTLA inhibitors

PD1 inhibitors

PD1 is a protein that is located on T lymphocytes (we have two types of white blood cells, B and T, for more read here) and has the ability to disable the immune system preventing it from fighting harmful agents if activated. In fact PD1 is a protein that is found on the surface of healthy cells, the reason of why immune system doesn't fight regular healthy cells within our body.

PDL1 inhibitors

Another protein exist on the surface of the cancer cells is PDL1 which can also send the stop message to  T cell lymphocytes to make them move away from the cancer cells. In this way, the cancer cells escape from the immune system.

CTLA4 inhibitors

Another protein on the surface of T lymphocytes that prevents the immune system from detecting cancer cells is called CTLA4. 

Today, monoclonal antibodies are made to bind directly to the PD1 or PDL1 proteins on cancer cells blocking their activity so that the immune system can recognize and destroy them. Some of these drugs include:

Inhibitors (PD1):

  • pembrolizumab (keytruda)
  • Nemolizumab (Opdivo)
  • Cemiplimab (Libtayo)

Inhibitors (PDL1):

  • atezolizumab (tecentriq)
  • Durvalumab (emphysema)

Inhibitors (CTLA 4):

  • ipilimumab

Unfortunately, these drugs has some side effects. Side effects of this class of drugs (checkpoint inhibitors) may include:

  • Diarrhea
  • Pneumonia
  • Skin rash
  • Itching
  • Hormonal changes   

Usually, the drug is stopped for a while only if the side effects are severe so that the body has a chance to recover.

 

Chimeric antigen receptors CAR T-cell therapy

In this method, a certain amount of blood is taken from a patient and its T lymphocytes are separated. Then in a sterile laboratory environment, specific man-made receptors are added to the surface of these T lymphocytes to increase their strength in attaching to cancer cells. These equipped T-lymphocytes from the patient's own blood cells, are returned to patients blood to begin identifying and fighting cancer cells. In this way, these T lymphocytes are equipped and strengthened to identify, bind and destroy cancer cells much better than regular T lymphocytes. This method is called gene therapy or immuno-effect cell therapy.

The mechanism of action of gene therapy

The cells of each type of cancer have their own characteristics identified with a small protein molecules called antigen. so T lymphocytes need a special receptor to attach to a particular cancer cell. Receptors on the surface of the T lymphocytes bind to antigens on the surface of the cancer cells and in this way the immune system targets these cell for destruction. Without this binding, defending the body against cancer will be impossible. In the method called CAR T-cell therapy, different man-made receptors carefully designed for each cancer are attached to the surface of the T cells helping them to attach to the targeted cancer cells.

In this process, the patient lies in bed and two IV lines are connected to his or her body. During the process of leukapheresis, white blood cells are separated and the rest of the blood returns to the patient's body through the second IV line. Next, T lymphocytes are removed from the white blood cells in the laboratory. Now, in a specialized chimeric laboratory, a proper receptor antigen suitable for the patient's cancer is added to the surface of T cells. These new T cells are called CAR T-cells. When (usually after a few weeks) a sufficient amount of CRT is available, the patient is called in to receive his/her infusion.

So far, the FDA has approved this method for a number of types of lymphoma and some types of leukemia. Among the approved types, the following products can be mentioned:

  • Leukocell tease (Chimeria)
  • Acisabetagen Cellulose (Yaskarta)
  • Brexucabtagene autoleucel (Tecartus)

CAR T-cell therapy side effects:

The side effects of the CAR T-cell therapy are severe fever, dangerous hypotension which are collectively called cytokine release syndrome, as well as neurotoxicity (toxicity to nerve cells) that can cause headacheseizure, cerebral edema and decreased consciousness.

 

Monoclonal antibodies

A series of proteins (antibodies) that are naturally made in our body by the immune system under certain defense conditions are now man-made and purified in advanced laboratories. These proteins are called monoclonal antibodies, which have different types of characteristics. They perform their job selectively meaning the can attack specific part of the cancer cell structure in a unique part of the body. In short, with immunotherapy, specific parts and functions of the human immune system are strengthened and used to fight diseases, including cancer, in a more targeted way. Nowadays, immune system products made in equipped laboratories have already been injected into patient's body and have been very effective in fighting cancer cells and diseases.

Antibodies are the product of the activity of the immune system in fighting the pathogen. To eliminate any antigen (a protein substance that is present on every cancer cell or any foreign agent), our body makes a special type of antibody that only destroys that particular type of antigen.

Today, in specialized laboratories, these types of antibodies are artificially made by researchers and are used in treatment of cancer. These drugs contain substances that are made specifically to fight the antigen on the cells of that specific type of cancer (Target therapy).

 

Types of monoclonal antibodies

  • Naked monoclonal antibodies
  • Monoclonal conjugated antibodies
  • Monoclonal bispecific antibodies

1) Naked monoclonal antibodies:

These are antibodies to which no drugs or radioactive substances have been attached. These are the most common types used to treat cancer:

  • Alemtuzumab (Compat) in the treatment of CLL
  • Trastuzumab (Herceptin) in the treatment of breast cancer (herto-positive) and gastric cancer

2) Monoclonal conjugated antibodies:

These antibodies are attached to chemotherapy drugs or radioactive particles. These substances circulate in the body to reach their target cell before starting to work.

Ibritumomab (Zevalin): It is attached to a radioactive particle and formed through the combination of Rituximab, which is a pure monoclonal antibody and a radioactive substance. These type of treatments are called radioimmunotherapy.

Brentuximab (Adcetris): built bya combination of a monoclonal antibody and a MMAI drug.

Ado-trastuzumab emtansine (Cadillac): Again, it is a combination of a pure antibody monoclonal with a chemotherapy drug that it is used in the treatment of Her2-positive breast cancers and some stomach cancers.

3) Bispecific monoclonal antibodies:

These compounds are composed of two different monoclonal antibodies, meaning that they can act specifically against two different antigens. for example, Blinatumomab (Blincyto) is used to treat a variety of leukemias and lymphomas.

 

monoclonal antibodies side effects:

Some of the side effects of monoclonal antibodies are:

Some types of monoclonal antibodies have side effects that are caused because of the cells they are targeting. For example:

bevacizumab (Avastin):

Which has a specific effect on the antigen that causes the growth of vascular tumors. Side effects of this drug include:

  • High blood pressure
  • Bleeding
  • Coagulation
  • Renal injury
  • Wound healing problems

Or Cetuximab (Erbitux) which targets an antigen called protein IGFR, which, in addition to the surface of cancer cells, is normally present on healthy skin cells. therefore, usage of this treatment is associated with very severe skin rashes.

 

Vaccines:

Vaccines stimulate the immune system to producing antibodies by inserting fragments of the pathogen. Different vaccine types are:

  • Preventive vaccines
  • Vaccines used to treat cancer 

 

Preventive vaccines

There are vaccines that can prevent cancer. For example:

  • The human papillomavirus vaccine activates the immune system against several types of the carcinogenic viruses. Vaccination in young children and adults protects them against cervical cancer and five HPV-related cancers.
  • A hepatitis B virus vaccine can prevent liver cancer. 

 

Vaccines used to treat cancer

These vaccines are made from pieces of cancer cells or their antigens. When entered into patient's body, they stimulate his or her immune system to fight the cancer. For example Sipuleucel (Provenge) is used to treat advanced prostate cancer. Side effects of this vaccine include fever, fatigue, joint pain, high blood pressure, and respiratory problems. Or Talimogene Laherparepvec is a vaccine used to treat skin melanoma. The vaccine is made from a type of herpes virus in the laboratory which can stimulate and strengthen the human immune system to defend against melanoma.

Cytokines:

Cytokines are substances (small proteins) that play a very important role in the growth and stimulation of our immune system. In other words, when cytokines are released in our body, signals for further activation are sent to the entire immune system. Interleukins, interferons, tumor necrosis factors, and growth factors are very important cytokines or chemokines. Today, some cytokines are made in laboratories and used to treat a wide range of diseases.

Interferons:

They have alpha, beta and gamma types and interferon alpha is the only interferon that is used in the treatment of cancers and the following diseases:

Some types of interferons are also used in autoimmune diseases such as MS.

Interleukins:

  • Interleukin II: Today it is made in laboratories and is used to treat kidney cancer and melanoma.
  • Interleukin II also accelerates the growth of immune system cells.

Immunomodulators:

Such as:

BCG bacteria:

This bacterium does not cause serious disease for humans, but it strongly stimulates the immune system. It is used today for treating the early stages of bladder cancer.

Imiquimod:

This drug is available in the market in the form of topical cream. This drug stimulates the local reaction of the immune system in the applied position and is effective at very early stages of skin cancers. It is also used in vitiligo which is an autoimmune skin disease. Today, special immunotherapy methods are used to treat and control autoimmune diseases such as MS, Graves and systemic lupus.

The US Food and Drug Administration has approved immunotherapy for a variety of non-Hodgkin's and Hodgkin's lymphomas in children and adults. Immunotherapy is one of the most promising treatments for lung cancer.

 

 

 

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