All About Immunotherapy

June is the month for ‘World Environment Day’, ‘Father s Day’, and ‘International Yoga Day’ and so is June also observed as `Cancer Immunotherapy Awareness Month`.

To spread awareness, Oncowin Cancer Center brings you easy access to very useful information on Immunotherapy- one of the breakthroughs in cancer therapy.

What is Immunotherapy ?

Immunotherapy also known as immune-oncology is a type of cancer treatment that helps the immune system fight against cancer.

[The immune system is made up of a network of cells & organs that protects the body from threats such as infections, toxins & abnormal cell development. The most common cells of the immune system are lymphocytes ( T cells, B cells & NK cells), neutrophils and monocytes/macrophages. These are types of white blood cells. The major proteins of the immune system are cytokines, antibodies (immunoglobulins) and complement proteins.]

Nowadays immunotherapy is ruling the roost in each step of cancer therapy. It uses substances made by the body or in a laboratory to boost the immune system and help the body find and destroy cancer cells.

Types of Immunotherapy

The different types of Immunotherapy include :

Monoclonal Antibodies & Immune Checkpoint Inhibitors

When the immune system detects something harmful, it makes antibodies. Antibodies are proteins that fight infection by attaching to antigens. Antigens are molecules that trigger the immune response in the body.

Monoclonal Antibodies are a type of protein that is made in the laboratory to boost the body’s natural antibodies or act as antibodies themselves. For example, they can be used to inhibit the activity of abnormal proteins in cancer cells. This is also considered a targeted therapy targeting cancer’s specific genes, proteins, or the tissue environment that helps the tumor grow and survive.

Immune Checkpoint Inhibitors are a type of immunotherapy that blocks the protein called immune checkpoints and thus boosts the immune system.

(Immune checkpoints are used by the body to naturally stop an immune system response and prevent the immune system from attacking healthy cells. Cancer cells can find ways to hide from the immune system by activating these checkpoints.)

Checkpoint inhibitors prevent cancer cells from blocking the immune system. Common checkpoints that these inhibitors affect are the PD-1/PD-L1 and CTLA-4 pathways.

Cancers that can be treated through Monoclonal Antibodies & Immune Checkpoint Inhibitors are

  • Bladder Cancer
  • Breast Cancer
  • Cervical Cancer
  • Head & Neck Cancer
  • Colorectal Cancer
  • Esophageal Cancer
  • Liver Cancer
  • Renal Cancer
  • Lung Cancer
  • Lymphoma
  • Melanoma
  • Non-Melanoma Skin Cancer

Non-specific Immunotherapy

Non-specific immunotherapy, also called non-specific immunomodulating agents, stimulate the immune system in a more general way. They don’t target cancer cells specifically. There are several kinds of non-specific immunotherapy that work in different ways

  • Cytokines: Cytokines are proteins that send messages between cells to activate the immune system. There are two types of cytokines used to treat cancer.

  • Interferons:

    Interferons are the proteins produced by immune system to alert the body that there is a pathogen, typically a virus, in the body. Interferons can be made in a laboratory to help the immune system fight cancer. They can also retard the growth of cancer cells. The most common type of interferon used in cancer treatment is called interferon alpha [Roferon-A (2a), Intron A (2b), Alferon (2a)].

  • Interleukins:

    Interleukins are the proteins that pass messages between cells. They also start an immune response.

    Examples – the lab made interleukin-2 (IL-2) or aldesleukin (proleukin)

  • Bacillus Calmette-Guerin (BCG): Bacillus Calmette-Guerin (BCG) is a vaccine that was originally used to prevent tuberculosis. Now it is also used to treat certain types of cancer.
    Cancer that can be treated through BCG-

    • Bladder Cancer

T-cell Therapy

A type of immunotherapy that is also known as adoptive cell therapy in which T cells (a type of immune cell) are given to a patient to help the body fight cancer. T cells are usually extracted from the patient’s own blood or tumor tissue, grown in a laboratory in large numbers, and then given back to the patient to help the immune system fight against the cancer. Sometimes, the T cells are changed in the laboratory so that they can better target the patient’s cancer cells and kill them.

Types of adoptive cell therapy-

  • Chimeric antigen receptor T-cell (CAR T-cell) therapy
  • Tumor-infiltrating lymphocyte (TIL) therapy
  • Bispecific T cell engager (BiTE)
  • Dual-affinity re-targeting (DART) antibodies

Adoptive cell therapy that uses T cells from a donor is being studied in the treatment of some types of cancer.

Cancer that can be treated through T-cell-

  • B-cell precursor acute lymphoblastic leukemia (ALL) in children & young adults up to age 25 years
  • Diffuse large B-cell lymphoma (DLBCL)
  • Primary mediastinal large B-cell lymphoma
  • Large B-cell lymphoma transformed from follicular lymphoma
  • High-grade B-cell lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Aggressive B-cell lymphoma not otherwise specified (NOS)
  • Multiple myeloma

Cancer Vaccine

A vaccine that stimulates the immune system to produce antibodies to fight cancer is known as a cancer vaccine.

Vaccines to prevent cancer

Preventive (prophylactic) vaccines are used to prevent viral infections that cause cancer or contribute to cancer development. They are designed to stimulate the immune system to attack certain viruses before they cause an infection. These vaccines are given to healthy people before cancer develops.

Human papillomavirus (HPV) vaccines protect against infection caused by certain types of HPV. These vaccines help protect against infection with types of HPV most commonly linked with precancerous conditions & cervical cancer.

Hepatitis is inflammation of the liver that can be caused by certain viruses. People with long-term infections with hepatitis B virus (HBV) are at a higher risk of liver cancer. Hepatitis B vaccines may lower the risk of developing liver cancer in some people.

Cancers that can be prevented through vaccines-

  • Related to HPV
    • Cervical cancer
    • Vaginal cancer
    • Vulvar cancer
    • Anal cancer
    • Penile cancer
    • Some Oral Cavity & Throat cancer
  • Related to HBV
    • Liver cancer

Vaccines to treat cancer

Cancer treatment vaccines can be made up of cancer cells, parts of cancer cells, or antigens. These vaccines stimulates the immune system to recognize and attack the cancer cells and thus eventually help to stop further growth of the cancer, prevent the recurrence of cancer and destroy cancer cells left behind after other treatments.

The following cancer treatments vaccines are most commonly studied,

  • Antigen vaccines are made from antigens in cancer cells.
  • Whole tumor vaccines use the whole cancer cell, not just an antigen, to make the vaccine. The vaccine is made from own cancer cells, cancer cells from another person, or cancer cells grown in a lab.
  • DNA vaccines are made with bits of DNA from cancer cells.
  • Dendritic cell vaccines are made from dendritic cells that are grown in a lab together with cancer cells.
  • Anti-idiotype vaccines stimulate the body to produce antibodies against cancer cells almost in the same way as antigen vaccines. An idiotype is the part of an antibody that determines the specific antigen the antibody will act against.

Patient selection criteria for Immunotherapy

Following factors are taken into consideration to initiate immunotherapy

  • Patient Age: Very elderly patients are generally not recommended immunotherapy because their immune system may not be in responsive state anymore & hence desired treatment goal may not be achieved.
  • Stage of Cancer: Stage of cancer also plays an important role in deciding the treatment plan. In some cases immunotherapy is suggested in the early stages & in some cases it is suggested in later stages too.
  • Genomic Testing: If genomic testing detects the biomarkers that are positive for PD-L1 expression, high microsatellite instability (MSI-H), or high tumor mutational burden (TMB-H) then immunotherapy may be opted.
  • Autoimmune Disorder: If a patient has an autoimmune disorder, they may be unable to tolerate immunotherapy even if otherwise they would have qualified for it.
  • Organ Transplant: If a patient has undergone an organ transplant, doctor may not suggest immunotherapy because of the already suppressed immune system the patient has.

Side effects of Immunotherapy

Different people have different side effects, also it depends on the type of immunotherapy received.

The known side effects are

  • Skin reactions at the needle site
    • Pain
    • Swelling
    • Soreness
    • Redness
    • Rash
    • Itchiness
  • Flu-like symptoms
    • Fever
    • Chills
    • Weakness
    • Fatigue
    • Dizziness
    • Nausea or vomiting
    • Muscle or joint pain
    • Headache
    • Trouble breathing
    • Low or high blood pressure
  • Other side effects
    • Swelling & weight gain from fluid retention
    • Heart palpitations
    • Sinus congestion
    • Infection
    • Organ inflammation
    • Diarrhea

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