Mesothelioma Immunotherapy

Mesothelioma immunotherapy is without doubt one of the most exciting new developments that has occurred in mesothelioma treatment in a long time.  Immunotherapy as a treatment option for all types of cancers stands to become the game-changing breakthrough we have all been hoping for in the fight against this terrible disease.

How Mesothelioma Immunotherapy Works

Mesothelioma immunotherapy works in a similar way to immunotherapy for other cancers. Basically, immunotherapy awakens a sleeping giant – the body’s own immune system – and mobilizes it to fight cancer.

Mesothelioma immunotherapy deploys your body’s good cells to fight the bad cells.  And as evil and deadly as cancer cells are, they are produced by your body. What better tool to fight them than other cells also produced by your body?  The body’s own immune cells may know how to help you best.

Chemotherapy and radiation involve one size-fits-all drugs. Up until now, this was the best weapon against cancer we had. But because these drugs are not as customized for your own body as your body’s own immune cells are, chemotherapy and radiation blast away, often killing many good cells along with the bad ones. This overkill mode is responsible for a lot of what we consider some of the worst side effects of cancer treatment. But even with immunotherapy, some drugs are still needed.

If your body’s immune system could just fight cancer all by itself, obviously it would have done so already. But unfortunately, cancer is so diabolically clever that it produces cells that are programmed to shut down your immune system. That’s where the exciting new class of immunotherapy drugs comes in.  They can break the spell and get your immune system fighting back at the top of its game.

Mesothelioma Immunotherapy Helps Cells Tell “Self” From “Non-Self”

Mesothelioma immunotherapy is a good strategy for battling cancer because it uses a patient’s own immune system to battle cancer.

A healthy immune system needs to do two basic jobs:

1) protect the body from foreign “non-self” cells and/or molecules

2) not attack “self” cells or molecules

Cancer cells are considered “non-self”.   Although they are human cells produced by your body, they’ve gone rogue. They are no longer playing by the rules that keep the body optimally functioning.  Cancer cells divide and multiply rapidly so the disease can take over the body, spreading even beyond the initial tumor site.

Through mutations in the DNA, cancer cells stop responding to cues to limit growth. That’s how tumors get started. If a tumor gets recognized as “non-self” by the immune system, it can be targeted for destruction.

How do immune cells know whether a cell is “self” or “non-self”?  They talk to the “hand” technically known as Major Histocompatibilty Complex, or MHC.

MHC is like a hand that sits on the cell membrane and “holds” a molecule.  This puts that molecule out there on the cell’s surface and on display to other cells in the body. This way the other cells get a clue to what molecules are present inside of it – kind of like goods on display in a store.

Sometimes stores don’t want you touching their display items but in this case, touching is the main idea. Immune system cells randomly bump into the MHC on these healthy cells and “touch” it to see what is being displayed. If the immune system cell “touches” the display often, it learns to recognize the presented molecule as a “self” cell.

The immune system has specific cells trained to recognize self, other cells that are trained to recognize “non-self” cells on the MHC.  And if “non-self” cells are detected, the battle begins with the immune system as the defending army with squadrons of specialized forces.

Some types of cells fight together to fend off the invader. Other cells bind to the invading or infected cells and kill them. And still other cells can secrete antibodies, which bind to the “non-self” cell on display on the MHC and neutralize it, or target it for destruction. Immune cells known as T cells transform into powerful Cytotoxic T cells, also known as CTL cells when activated.  CTL cells are a type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus. CTL cells are the ones that attack the tumor and cause it to shrink.

How Do Tumor Cells Evade the Body’s Immune System?

War is also a matter of strategy and not just firepower alone. And the war between cancer cells and your immune system cells is no different. Both sides have developed strategies to outsmart the other.

Just as the immune system has figured out how to defend itself against tumors it determines are non- self, tumors have figured out how to evade detection by the immune system.

Because tumors are made up of thousands of individual cells, not all of them look exactly alike. Many are recognized by the immune system but some are not. While your activated CTL cells are busy battling it out with the tumor cells they recognize and are trying to destroy, other unrecognized tumor cells are slipping past them undetected.  They are then free to divide and grow more tumor cells. Sometimes the immune system’s army just gets outnumbered and can’t keep up.

Some tumor cells also pack a powerful weapon that can paralyze the body’s immune cells and render them helpless in the fight against cancer. They activate pathways that trip up the immune system’s T cells. They do this by producing an immune cell-suppressing protein called PD-1. PD-1 is an abbreviation for “programmed cell death protein 1.”  It sounds evil because it is. When the immune system’s cells are suppressed by PD-1, it is like they are asleep and cancer cells get a free pass at running rampant destroying healthy cells.

What New Mesothelioma Immunotherapy Treatments Have Been Developed?

Mesothelioma immunotherapy can be both passive and active. In passive mesothelioma immunotherapy, components that can help boost the immune system are injected into the body. In active mesothelioma immunotherapy, direct intervention is strategically used to help rev up parts of the immune system; specifically, key parts that are being suppressed by cancer cells to prevent the immune system from fighting back.

We’ll explore these different approaches to mesothelioma immunotherapy:

Antibody Therapy – Antibody therapy is one of the more passive ways mesothelioma immunotherapy can help.  It works is by taking some of the helpful things immune system cells can do and duplicating them in the lab. Then these mesothelioma immunotherapy helpers made in the lab can be injected into the body to give the overwhelmed immune system a boost with helpful reinforcements.

For example, some immune system cells produce antibodies to neutralize harmful invaders. Researchers can also create those antibodies in the lab. Then these new synthetic antibodies are injected into a person with cancer. The new lab-made antibodies will bind to a molecule that relates to a specific type of tumor. That is like sending out a signal to other immune system cells saying, “Bad guy over here. Come and destroy!” So then that tumor gets targeted for destruction by the immune system. In some cases, the antibody can be attached to a toxin before it is injected into the patient. The antibody will go to the tumor and bring the toxin with it.  This causes death to the tumor cells while not harming the body’s healthy tissue.

How this works for mesothelioma immunotherapy – Some antibodies can be used to help deliver drugs that work against molecules that are found only in mesothelioma tumors. If researchers can attach a mesothelioma treatment to the antibody, it would attack only the tumor, and not affect the surrounding tissues.

Adaptive Cellular Therapy – This type of mesothelioma immunotherapy echoes some elements of a basic school lab experiment.  The immune system cells are losing the war against cancer cells because they are vastly outnumbered.  The body is making all the immune cells it can but it is not enough.  The solution?  Make more in the laboratory.  Scientists remove T cells from patients, culture them and grow more of them in a Petri dish. The reinforcement of new T cells can then come to the rescue by being injected into the patient. This technique can be used in mesothelioma, particularly in combination with the vaccination strategy described below.

Vaccination – This works just like the vaccinations for other illnesses. Some diseased cells are injected in an amount small enough not to cause illness but big enough to trigger the body’s immune system into action. Once the immune cells have been activated against a particular illness, they will remember it and act as security guards protecting against it.  This is the reason for vaccinating against disease like polio and smallpox. With cancer, tumor cells are removed, killed and then re-injected to help train immune system cells to attack live tumor cells.

How this works for mesothelioma immunotherapy – The vaccination technique is now being used to increase the body’s immune response to mesothelioma. A mesothelioma tumor is biopsied and then the cells are put in a petri dish with immature immune system cells.  When the cells mature, they are now primed to fight the tumor. These new tumor-fighting cells are then injected into the patient.

Checkpoint Blockade – This defense works on the ability of some tumor cells to suppress the immune system.  These tumor cells produce an immune-suppressing protein called PD-1, which again is short for “programmed cell death protein 1.” They can successfully shut down the immune system so its cancer cell buddies can do their worst. Checkpoint blockade therapy counteracts this. It activates the immune response by blocking checkpoints like PD-1.

How this works for mesothelioma immunotherapy – Only about 20 – 40 percent of mesothelioma tumors are affected by PD-1. Research is currently underway to produce a checkpoint blockade drug that specifically will help prevent mesothelioma tumor cells from suppressing the active form of T cells.

Cytokine therapy: Another way of boosting the immune system is to encourage the immune system to produce cytokines. These are inflammatory substances that cause T cells to activate.

How this works for mesothelioma immunotherapy:  In theory, cytokines simply need to be delivered to the tumor using surgical techniques.  In reality, it is not so easy.  Because of mesothelioma’s usual location inside the linings of the lungs within the chest cavity, it is a difficult area to reach directly with drugs. Viruses are being studied as a way to deliver cytokines. The viruses would be incapable of causing an infection in the traditional sense, but are able to insert themselves into tumor cells.