What is cancer immunotherapy and how does it work?

Immunotherapy is a cancer treatment in which your immune system fights cancer cells. Actually, the term immunotherapy is widely used for a set of different treatment strategies that alter the body's immune response or use substances produced by the immune system to attack cancer cells. These treatments are known as biological therapies.

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How Immunotherapy Works

The theory behind immunotherapy is that your immune system already knows how to fight cancer. Just as your body can identify, tag, and create an immune response against invading bacteria and viruses, cancer cells can also be marked abnormal and killed by the immune system.

The concept of immunotherapy has been around for a long time. A century ago, a doctor named William Kohli noted that some patients, when infected with bacteria, appear to be fighting cancer. Another doctor named Steven Rosenberg asked questions about the immune system-based approach to cancer treatment .

In rare cases, the cancer can go away without treatment. This remission or spontaneous regression of the cancer has been documented, although it is very rare. Dr. Rosenberg's theory was that his patient's immune system attacked and cured cancer.

Although there are many different types of immune cells and molecular pathways that lead to the elimination of cancer cells, the "big weapons" in the fight against cancer are T cells (T lymphocytes) and natural killer cells .

The immune system must perform several tasks to attack cancer cells. Simply put, these include:

  • Remark :   The immune system must first find and identify cancer cells. (An analogy could be made with a forester walking through a forest looking for diseased trees.)
  • Marking : Once detected, our immune system must mark or mark cancer cells for destruction. (Similar to how a forest worker marks problem trees with spray paint.)
  • Signaling : Once cancer cells are tagged, immune cells must sound an alarm, attracting cancer-fighting cells to the region. (Think of that forestry worker now calling your team.)
  • Fight : Once this happens, T cells and natural killer cells attack and kill cancer cells in the body (such as workers who cut and uproot diseased trees).

Obviously, there are not enough immune cells to deal with cancer on their own. If they were, the cancer would not be fatal.

Many cancers have the ability to dodge or disguise themselves so that their body does not recognize them as a threat. Cancer cells can hide :

  • Decreased expression of antigens on the cell surface.
  • Production of molecules that inhibit the immune response.
  • It causes nearby non-cancer cells to secrete substances that reduce the effectiveness of the immune system. This approach is called "changing the microenvironment," that is, the area around cancer cells.

Immunotherapy drugs use many functions to help the immune system find and attack cancer cells once and for all. These include :

  • Help the immune system recognize cancer
  • Activation and strengthening of immune cells.
  • Interference with a cancer cell's ability to hide (unmask)
  • Interfere with the cancer cell microenvironment by altering cancer cell signals.
  • Using the principles of the immune system as a model for developing anticancer drugs

How immunotherapy differs from other cancer treatments

Unlike many advancements in oncology based on previous therapies, immunotherapy is basically a completely new way of treating cancer (nonspecific immunomodulators like interferon have been around for decades).

Compared to many other treatments :

  • Some immunotherapy treatments can work for different types of cancer (for example, melanoma and lung cancer).
  • Some of these therapies may work for more advanced and untreatable cancers (such as advanced lung cancer or pancreatic cancer).
  • In some cases, there can be long-lasting results, what oncologists call a sustainable response. Most solid tumor cancer therapies, such as chemotherapy and drugs that target specific genetic changes in cancer cells, are limited; cancer cells eventually become resistant to treatment.

Advancement in cancer

Immunotherapy has been named Achievement of the Year in Clinical Oncology Practice 2016 by the American Society for Clinical Oncology. For people with cancer, this area, along with advances in treatment such as targeted therapy, is an occasion for a sense of hope, not just for the future, but for the present.

Types

You may have heard that immunotherapy is described as a treatment that "strengthens" the immune system. In reality, these treatments are much more complex. Methods currently approved or evaluated in clinical trials include the following .

Monoclonal antibodies (therapeutic antibodies)

Monoclonal antibodies work by targeting cancer cells and have been used for more than 20 years, especially in some types of lymphoma .

Therapeutic or monoclonal antibodies are "artificial" antibodies designed to attack cancer cells instead of microorganisms. They stick to antigens (protein markers) on the surface of cancer cells, essentially marking them. Once cancer cells are labeled in this way, other cells of the immune system know how to destroy them.

Instead, another type of monoclonal antibody can bind to cancer cell antigen to block the growth signal from reaching the receptor. When this happens, the growth signal cannot get the access it needs to tell the cancer cell to divide and grow.

Medications that deliver monoclonal antibodies include:

  • Avastin (bevacizumab)
  • Herceptin (trastuzumab)
  • Rituxan (rituximab)
  • Vectibix (panitumumab)
  • Erbitux (cetuximab)
  • Gazywa (obinutuzumab)

Another type of monoclonal antibodies are bispecific antibodies. These antibodies bind to two different antigens. One marks the cancer cell and the other activates the T cell and unifies them. An example is Blincyto (blinatumomab).

Conjugated monoclonal antibodies

The above monoclonal antibodies work on their own, but the antibodies can also bind to a chemotherapeutic drug, toxic substance, or radioactive particle in a treatment called conjugated monoclonal antibodies.

The word conjugate means "attached." In this situation, the attached "payload" is sent directly to the cancer cell. If the antibody binds to the cancer cell antigen and delivers the treatment directly to the source, the healthy tissue may be less damaged .

Some FDA-approved drugs in this category include:

  • Kadsila (ado-trastuzumab)
  • Adcetris (brentuximab vedotin)
  • Zevalin (ibritumomab tuxetan)
  • Ontac (Denileukin Difitox)

Immune checkpoint inhibitors

The immune system has a system of checks and balances, so it does not work with excess or delay. To prevent the former, which can cause an autoimmune disease like rheumatoid arthritis, there are inhibitory checkpoints along the immune pathway that act as brakes that slow the car down.

But, as mentioned, cancer cells can be sneaky and deceptive. One way to do this is to use control proteins, substances that suppress or slow down the immune system. Because cancer cells arise from normal cells, they have the ability to make these proteins; some simply find a way to use them abnormally to avoid detection. As a result, proteins suppress the immune system.

Immune checkpoint inhibitors to combat this. They can bind to these checkpoint proteins and release the brakes so the immune system can get back to work and fight cancer cells.

Examples of checkpoint inhibitors currently in use include:

  • Opdivo (nivolumab)
  • Keytruda (pembrolizumab)
  • Ervoy (ipilimumab)

Research is currently underway to examine the benefits of combining two or more drugs in this category. For example, the combined use of PD-1 and CTLA-4 inhibitors (Opdivo and Yervoy) is promising .

It is important to note that these treatments can overlap. For example, a drug used as a checkpoint inhibitor can also be a monoclonal antibody.

Adoptive cell transfer

One of the reasons the immune system does not fight large tumors is because it is simply suppressed. Imagine 10 soldiers fighting in the front line against 100,000 opponents.

Acceptable cell transfer techniques strengthen your defenses. Doctors first remove your T cells from the area around the tumor. After the T cells are collected, they are grown in a laboratory. Once they have multiplied enough, they are reintroduced into your body.

This treatment has led to a cure for some people with melanoma .

CAR T cell therapy

CAR T-cell therapy may be thought to "tune in" the immune system. CAR stands for chimeric antigen receptor; chimeric means "bound". In this therapy, your own T cells are harvested and then modified to express CAR.

This receptor allows your T cells to bind to receptors on the surface of cancer cells to kill them. In other words, it helps T cells to recognize cancer cells.

CAR T cell therapy

Two CAR T-cell drugs have received FDA approval: Yescarta and Kymriah.

  • Yescarta (axicabtagene ciloleucel) is a T-cell therapy that uses a chimeric antigen receptor (CAR) and is used to treat adults with certain types of large B-cell lymphoma that have not responded or have relapsed after at least one other two treatments.
  • Kymriah (tisagenlecleucel) is used in pediatric and adult patients with recurrent or refractory acute lymphoblastic leukemia, and in adult patients with some types of recurrent or refractory large B-cell lymphoma after two or more lines of systemic therapy.

Cancer vaccines

Cancer vaccines are immunizations that trigger an immune response to cancer. You may hear about vaccines that can help prevent cancer, such as hepatitis B and HPV, but cancer vaccines are used for a different purpose: to attack cancer that is already present.

When you are immunized against, for example, tetanus, your immune system is exposed to a small amount of inactivated tetanus toxin. Seeing this, your body recognizes it as foreign, injects it into a B cell (B lymphocyte), which then produces antibodies. If you later contract tetanus, your immune system will be ready to attack.

The approach is similar: Cancer vaccines can be made using tumor cells or the substances they make.

An example of a cancer vaccine used in the United States is Provenge (sipuleucel-T) to treat prostate cancer. Cancer vaccines are currently being tested for various types of cancer and to prevent breast cancer recurrence.

For lung cancer, two different vaccines, CIMAvax EGF and Vaxira (racotumomab-alum), have been studied in Cuba against non-small cell lung cancer. These vaccines, which have been found to increase progression-free survival in some people with non-small cell lung cancer , are also beginning to be studied in the United States .

Depending on the treatment, immunotherapy drugs can be given intravenously, orally, topically (cream), or intravesically (into the bladder).

Oncolytic viruses

The use of oncolytic viruses is also called cancer cell dynamite. When many people think of viruses, they generally think of something bad. Viruses, like the common cold, infect the body by entering cells, multiplying, and eventually causing them to explode. Oncolytic viruses are used to "infect" cancer cells. In this case, such a development of events can be beneficial.

These treatments work in different ways. In addition to the above, they also release antigens into the bloodstream, which attract more immune cells to attack.

Thalimogen laherparepvec (T-VEC or Imlygic) is the first oncolytic virus approved by the FDA. This virus can attack both cancer cells and normal cells, but unlike cancer cells, normal cells can survive .

Cytokines (immune system modulators)

Immune system modulators are a form of immunotherapy that has been available for many years. These treatments are called nonspecific immunotherapy. In other words, they help the immune system fight any invaders, including cancer.

These immunoregulatory substances, cytokines , which include both interleukins (IL) and interferons (IFN), enhance the ability of immune cells to fight cancer.

Examples include IL-2 and IFN-alpha, which are used in kidney cancer and melanoma, among other cancers.

Adjuvant immunotherapy

Bacillus Calmette-Guerin (BCG) vaccine is a currently approved form of adjuvant immunotherapy for the treatment of cancer ( adjuvant means something that enhances the body's immune response to an invader). In some parts of the world, it is used to protect against tuberculosis, although it has also been used successfully to treat bladder cancer.

Instead of being immunized, the vaccine is injected into the bladder, where it elicits an anticancer response .

Side effects

Because immunotherapy specifically targets cancer, the researchers expected these treatments to have fewer side effects than traditional chemotherapy drugs. However, like all cancer treatments, immunotherapy drugs can cause adverse reactions that depend on the category of immunotherapy and the specific drugs. They can range from mild to severe.

Some of the side effects include :

  • Skin reactions: the skin can be sensitive to sunlight. Redness, blisters, and itching are common; scratching the skin can lead to infection. Fingers are particularly prone to irritation with blisters and cracks on the fingertips and around the nails.
  • Flu-like symptoms: fever, nausea, body aches.
  • Inflammatory conditions : The colon, lungs, and heart muscle can be susceptible to irritation, a sign of an overactive immune response.
  • Muscle pain
  • Difficulty breathing
  • Cardiopalmus
  • Bloating (water retention) and weight gain.

Contraindications

Because immunotherapy is so new, there are no clinical studies that reliably indicate who should not receive it for cancer treatment due to dangerous or life-threatening side effects. But doctors are learning.

For example, immunotherapy can increase the risk or severity of tuberculosis, but these cases have been incredibly rare. In another case, a 47-year-old woman spontaneously developed type 1 diabetes in adults three weeks after a single course of immunotherapy. But again, this was an isolated incident .

With time for proper investigation and observation, general contraindications, if any, will become apparent in the years to come.

Get the word of drug information

The field of immunotherapy is impressive, but it is in its infancy and still has a lot to learn. At this stage of development, it is important to be aware of some of the limitations of immunotherapy.

However, some patients had positive results. If you are diagnosed with cancer, your oncologist will be able to determine if you are eligible for immunotherapy and if so, which one.

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