What Types Of Cancer Can Be Treated With Immunotherapy?

Immunotherapy is a cancer treatment that uses your immune system to fight malignant cells. The term immunotherapy is actually used broadly for a collection of varying treatment strategies that alter the body’s immune response or use substances made by the immune system to target cancer cells. These treatments are known as biologic therapies.

How Immunotherapy Works

The theory behind immunotherapy is that your immune system already knows how to fight cancer. Just as your body is able to identify, label, and mount an immune response against bacteria and viruses that invade it, cancer cells may also be tagged as abnormal and eliminated by the immune system.

The concept of immunotherapy has been around for a long time. A century ago, a physician known as William Coley noted that some patients, when infected with a bacterium, appeared to fight off their cancers. Another physician named Steven Rosenberg is credited with asking questions about an immune system-based approach to cancer.1

On rare occasions, cancer may resolve itself without any treatment. This spontaneous remission or regression of cancer has been documented, although it is very rare. Dr. Rosenberg’s theory was that his patient’s immune system had attacked and cleared the cancer.

While there are many different types of immune cells and molecular pathways that result in the removal of cancer cells, the “big guns” in fighting cancer are T-cells (T lymphocytes) and natural killer cells.

The immune system needs to perform multiple tasks to target cancer cells. In simple terms, these include:

• Surveillance: The immune system first needs to find and identify cancer cells. (An analogy would be a forestry worker walking through the forest looking for diseased trees.)
• Tagging: Once discovered, our immune system needs to mark or label cancer cells for destruction. (Akin to the forestry worker tagging problematic trees with spray paint.)
• Signaling: Once cancer cells are marked, immune cells need to sound an alarm, attracting cancer-fighting cells to the region. (Think of that forestry worker now calling in their crew.)
• Fighting: Once the above occurs, T cells and natural killer cells attack and remove cancer cells from the body (much like the workers cutting down and hauling away the diseased trees).

Obviously, immune cells are not enough to take care of cancer all by themselves. If they were, cancer wouldn’t be lethal.

Many cancers are able to evade or disguise themselves so your body doesn’t recognize them as a threat. Cancer cells may hide by:2

• Decreasing the expression of antigens on the surface of the cells
• Producing molecules which depress the immune response
• Causing nearby non-cancer cells to secrete substances that reduce the effectiveness of the immune system. This approach is referred to as “altering the microenvironment,” the area surrounding the cancer cells.

Immunotherapy medications use a variety of functions to help the immune system find and target cancer cells once and for all. They include:3

• Helping the immune system recognize cancer
• Activating and amplifying immune cells
• Interfering with a cancer cell’s ability to hide (de-masking)
• Interfering with the microenvironment of cancer cells by altering cancer cell signals
• Using the principles of the immune system as a template for designing cancer drugs

How Immunotherapy Differs From Other Cancer Treatments

Unlike many advances in oncology which build upon earlier treatments, immunotherapy is mostly an entirely new way to treat cancer (non-specific immune modulators, such as interferon, have been around a few decades).

Compared to many other treatments:2

• Some immunotherapy treatments may work across cancer types (say, for melanoma and lung cancer).
• Some of these treatments may work for the most advanced and hardest-to-treat cancers (e.g., advanced stage lung cancer or pancreatic cancer).
• Some cases may have lasting results—what oncologists refer to as a durable response. Most cancer treatments for solid tumors, such as chemotherapy, and drugs that target specific genetic changes in cancer cells, are limited; cancer cells eventually become resistant to the treatment.

Types

You may have heard immunotherapy described as a treatment that “boosts” the immune system. These treatments are actually much more complex. Methods currently approved or being evaluated in clinical trials include the following.3

Monoclonal Antibodies (Therapeutic Antibodies)

Monoclonal antibodies work by making cancer cells a target and have been used for more than 20 years, especially for some types of lymphoma.5

Therapeutic or monoclonal antibodies are “man-made” antibodies designed to attack cancer cells rather than microorganisms. They attach to antigens (protein markers) on the surface of cancer cells, essentially marking them. Once the cancer cells are so tagged, other cells in the immune system know to destroy them.

Another type of monoclonal antibody may instead attach to an antigen on a cancer cell in order to block a growth signal from reaching a receptor. When this occurs, the growth signal cannot gain 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)
• Gazyva (obinutuzumab)

Another type of monoclonal antibody is a bispecific antibody. These antibodies bind to two different antigens. One tags the cancer cell and the other works to recruit a T cell and bring the two together. An example is Blincyto (blinatumomab).

Conjugated Monoclonal Antibodies

The monoclonal antibodies above work alone, but antibodies may also be attached to a chemotherapy drug, a toxic substance, or a radioactive particle in a treatment method called conjugated monoclonal antibodies.

The word conjugated means “attached.” In this situation, an attached “payload” is delivered directly to a cancer cell. By having an antibody attach to an antigen on a cancer cell and deliver the treatment directly to the source, there can be less damage to healthy tissues.6

Some medication in this category approved by the U.S. Food and Drug Administration (FDA) include:

• Kadcyla (ado-trastuzumab)
• Adcetris (brentuximab vedotin)
• Zevalin (ibritumomab tiuxetan)
• Ontak (denileukin difitox)

Immune Checkpoint Inhibitors

The immune system has checks and balances so that it doesn’t overperform or underperform. In order to prevent the former—which can cause an autoimmune disease like rheumatoid arthritis—there are inhibitory checkpoints along the immune pathway that work like brakes to slow a car.

But, as stated, cancer cells can be tricky and deceptive. One way they do this is via checkpoint proteins, the substances that suppress or slow down the immune system. Since cancer cells arise from normal cells, they have the ability to make these proteins—some just find a way to use them abnormally to escape detection. As a result, the proteins end up slamming the brakes on the immune system.

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

Examples of checkpoint inhibitors currently being used include:

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

Research is now looking into the benefits of combining two or more drugs in this category. For example, using PD-1 and CTLA-4 inhibitors together (Opdivo and Yervoy) is showing promise.7

Adoptive Cell Transfer

One of the reasons the immune system doesn’t fight off large tumors is that it’s simply overpowered. Think of having 10 soldiers on the front lines going against 100,000 opponents.

Adoptive cell transfer treatments work to bolster your defense force. Doctors first remove your T cells from the region surrounding your tumor. Once your T cells are collected, they are grown in the lab. After they’ve sufficiently multiplied, they are then injected back into your body.

This treatment has resulted in a cure for some people with melanoma.8

CAR T-Cell Therapy

CAR T-cell therapy may be thought of as an immune system “tune-up.” CAR stands for chimeric antigen receptor; chimeric means “joined together.” In this therapy, your own T cells are collected and then modified to express a CAR.

This receptor allows your T cells to attach to receptors on the surface of cancer cells to destroy them. In other words, it assists your T cells in recognizing the cancer cells.

No CAR T-cell therapies are approved yet, but they are being tested in clinical trials with encouraging results, especially against leukemia and melanoma.9

Cancer Treatment Vaccines

Cancer vaccines are immunizations that jumpstart the immune response to cancer. You may hear of vaccines that can help prevent cancer, such as hepatitis B and HPV, but cancer treatment vaccines are used with a different goal: to attack a cancer that’s already present.

When you are immunized against, say, tetanus, your immune system is exposed to a small amount of inactivated tetanus toxin. In seeing this, your body recognizes it as foreign, introduces it to a B cell (B-lymphocyte) which then produces antibodies. If you are exposed to tetanus later, your immune system is primed and ready to attack.

The approach here is similar: Cancer vaccines may be made using either tumor cells or substances they produce.

An example of a cancer treatment vaccine used in the United States is Provenge (sipuleucel-T) for prostate cancer.10 Cancer vaccines are currently being tested for several cancers, as well as to prevent breast cancer recurrence.

With lung cancer, two separate vaccines—CIMAvax EGF and Vaxira (racotumomab-alum)—have been studied in Cuba for 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 beginning to be studied in the United States as well.11

Oncolytic Viruses

The use of oncolytic viruses has been referred to analogously as “dynamite for cancer cells.” When many think of viruses, they usually think of something bad. Viruses such as the common cold infect the body by entering cells, multiplying, and eventually causing the cells to burst. Oncolytic viruses are used to “infect” cancer cells. In this case, this progression of events can be beneficial.

These treatments appear to work in a few ways. In addition to the above, they also release antigens into the bloodstream that attract more immune cells to come and attack.

Talimogene laherparepvec (T-VEC, or Imlygic) is the first FDA-approved oncolytic virus. This virus can attack both cancer and normal cells, but unlike the cancer cells, the normal cells are capable of surviving.10

Cytokines (Immune System Modulators)

Immune system modulators are a form of immunotherapy that has been available for many years. These treatments are referred to as non-specific immunotherapy. In other words, they work to help the immune system fight off any invader, including cancer.

These immunoregulatory substances—cytokines, including both interleukins (ILs) and interferons (IFNs)—accentuate the ability of immune cells to fight cancer.

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

Adjuvant Immunotherapy

The Bacillus Calmette-Guerin (BCG) vaccine is one form of adjuvant immunotherapy that is currently approved for treating cancer (adjuvant means something that strengthens the body’s immune response to an invader). It’s used in some parts of the world as protection against tuberculosis, though it has also been successfully used to treat bladder cancer.

The vaccine, instead of being given as an immunization, is injected into the bladder where it produces a cancer-fighting response.12

Side Effects

Because immunotherapy addresses cancer specifically, scientists hoped that these treatments would have fewer side effects than traditional chemotherapy drugs. Like all cancer therapies, however, immunotherapy medications can result in adverse reactions that vary depending on the category of immunotherapy as well as the particular medications. They can be mild to severe.

Some side effects include:13

• Skin reactions: Skin can be sensitive to sunlight. Redness, blistering, and itching can be common; breaking the skin by scratching may cause an infection. Fingers are especially susceptible to irritation with blistering and cracking possible on fingertips and around the fingernails.
• Flu-like symptoms: Fever, nausea, body aches
• Inflammatory conditions:14

  The colon, lungs, and heart muscle can be susceptible to irritation—a sign of an overactive immune response.

• Muscle aches
• Shortness of breath
• Heart palpitations
• Edema (water retention) and weight gain

Contraindications

Because immunotherapy is so new, clinical research does not yet exist that confidently indicates who should not receive it for cancer treatment because of 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 adult-onset type 1 diabetes three weeks after receiving a single immunotherapy treatment. But again, this was an isolated case.15

Given time for proper research and observation, common contraindications, if any, will come into focus in the years to come.