• Immunotherapy is defined as one of the methods of treatment by inducing, enhancing, or suppressing an immune response.
• It is one of the types of biological therapy in which the substances obtained from living organisms are used to treat cancer.
• Generally, immunotherapies are classified into two groups:
  • Activation immunotherapies: includes immunotherapies employed for amplifying an immune response.
  • Suppression immunotherapies: includes immunotherapies that suppress or reduce an immune response.
• Mostly, immunotherapies have been found to be promising to cure varieties of cancer.
• Also, it often has fewer side effects in comparison to the existing drugs.

Relation between immunotherapy and immune system:

• Immunotherapy helps to enhance immune cells by providing with additional components.
• Immunotherapy instructs the immune system to identify and defend specific cancer cells.
• Immunotherapy helps to eradicate cancer by boosting immune cells.

Types of Immunotherapy for cancer:

There are various types of immunotherapy. They are listed as follows:

1. Monoclonal antibodies and tumor-agnostic treatments, such as checkpoint inhibitors
2. Oncolytic virus therapy
3.  CAR T-cell therapy
4. Cancer vaccines
5. Immune checkpoint inhibitors

1. Monoclonal antibodies (mAbs or MoAbs) and tumor-agnostic treatments:

• When a threat is sensed by the immune system, it produces antibodies.
• Antibodies are proteins that interact with antigens and initiate an immune response in the body.
• Monoclonal antibodies are defined as antibodies that are prepared in laboratory in order to boost the natural antibodies or to defend the foreign threats itself.
• Monoclonal antibodies help to fight cancer in several ways, for instance, monoclonal antibodies can be designed to fight with a specific cancer cell.
• Thus, it is also termed as targeted therapy.
• Basically, three types of mAbs are introduced, they are:
  • i. Naked monoclonal antibodies:
    • Most commonly used for treatment of cancer.
    • They are not attached to any other substance.
    • These antibodies instruct the immune system to defend cancer cells or block proteins within tumor.
  • ii. Conjugated monoclonal antibodies:
    • These are attached with either a radioactive particle or chemotherapy drug.
    • They are capable of attaching directly to the cancer cells.
    • It works by delivering the drug to the location of utmost requirement.
    • There are reduced or less chance of side effects and enhances the chemotherapy as well as radiation.
  • iii. Bispecific monoclonal antibodies (BsMAb):
    • These are antibodies designed in order to bind with two proteins at once.
    • Few can bind to both cancer cells and an immune system cell facilitating the immune response on cancer.

2. Oncolytic virus therapy:

• In this type of treatment, viruses used are modified in the lab with a motive to infect and kill specific tumor cells.
• Procedure of Oncolytic virus therapy:
  • First, the genetically modified virus is injected into the tumor.
  • Then the virus reaches the cancer cells and make copy of itself.
  • This leads to the disruption of cancer cells and ultimately their death.
  • As soon as the cells die, it stimulates the immune system to attack any cancer cells on the body having alike proteins as that of dead cells.
• This modified oncolytic virus doesn’t affect healthy cells.
• This therapy is considered superior to all other immunotherapies as it does not depend on any specific antigen expression patterns.
• The features that makes it an ideal candidate for the treatment of diverse malignancies are as follows:
  • Oncolytic viruses enhance the recruitment of tumor-infiltrating lymphocytes (TILs)
  • Reprogramming of immunosuppressive tumor micro-environment (TME)
  • Boosts systemic anti-tumor immunity

 3. CAR T-cell therapy:

• It stands for chimeric antigen receptor T-cell therapy (CAR T-cell therapy).
• T cell, a type of leukocytes is one of the main constituents of the adaptive immune system.
• In CAR T-cell therapy, the doctor reprograms T cells after taking out T cells from blood in order to find cancer cells more easily in contrast to it, T-cell therapy instruct the T-cells to search for tiny bits of specific antigens inside the cancer cells.
• Procedure of CAR T-cell therapy:
  • At first T cells are isolated from patient’s blood.
  • Then, the receptors, which are specific proteins are added to it in the laboratory.
  • The receptors permit the T cells to identify cancer cells.
  • Then, the programmed T cells are then re-entered into the body.
  • Now, these cells find and destroy cancer cells.
• Side effects such as low blood pressure, fever, confusion, and in rare cases, seizures are observed.

4. Cancer vaccines:

• These are also termed as therapeutic vaccines.
• The vaccines are employed to people already diagnosed with cancer with a motive to increase body’s natural defense in order to fight cancer.
• The vaccines may either prevent the cancer from recurrence, destroy any cancer cells remnant even after the accomplishment of other treatments or stop a tumor from spreading.
• Procedure of cancer vaccine therapy:
  • As we know, when the antibodies are produced in response to the antigens, the immune system develops memory cells, which will respond to these antigens in future.
  • Cancer vaccines enhance the immune system’s capacity to identify and destroy antigens.
  • Certain molecules termed as cancer specific antigens are present on the surface of the cancer cells, which are lacked by healthy cells.
  • These molecules act as antigens when given to a person, and trigger the immune system to identify and kill cancer cells having these molecules on the surface.
  • Few cancer vaccines also consist of adjuvants that may enhance the immune response.

5. Immune-checkpoint inhibitors:

• It is the significant function of immune cells to be able to differentiate between the own normal cells and foreign cells.
• Checkpoints are thus required, in order to monitor the foreign cells.
• In general term, immune checkpoints are molecules on specific immune cells that needs to be either activated or inactivated for starting an immune response.
• Drugs targeting these checkpoints are found to be promising for cancer treatment.
• These drugs are hence termed as checkpoint inhibitors.
• Two types of checkpoint inhibitors are described on the basis of proteins they target, they are:
• i. Checkpoint inhibitors that target PD-1 or PD-L1:
  • T cells are immune cells and PD-1 is a checkpoint protein on it.
  • PD-1 protein prevents the T-cells from attacking other cells in the body, acting as a type of off switch.
  • It occurs when it is bound to PD-L1, which is a protein on some normal and cancer cells.
  • After the binding, it stops T-cells from attacking any cells favoring the cancer cells with high PD-L1 protecting it from immune attack.
  • Monoclonal antibodies targeting either PD-1 cells or PD-L1 cells can prevent the binding and enhance immune response against cancer cells.
    • Drugs targeting PD-1 (PD-1 inhibitors):
      • Pembrolizumab (Keytruda)
      • Nivolumab (Opdivo)
      • Cemiplimab (Libtayo)
    • Drugs targeting PD-L1 (PD-L1 inhibitors):
      • Atezolizumab (Tecentriq)
      • Avelumab (Bavencio)
      • Durvalumab (Imfinzi)
• ii. Checkpoint inhibitors that target CTLA-4
  • Some T cells contain CTLA-4 protein that also acts as a off switch inorder to regulate immune system.
  • The CTLA-4 is inhibited by Ipilimumab (Yervoy) which is a monoclonal antibody that attaches to CTLA-4.
  • The body’s immune response is hence improved.
  • This drug is proved to treat melanoma of skin.
• Side effects of checkpoint inhibitors include:
  • – Inflammation in the lungs
  • – Rashes along with itchiness
  • – Kidney infections
  • – Diarrhea

Immunotherapy-Types of Immunotherapy for cancer

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