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Issue 4 Understanding Science

Using our own body to fight cancer – the era of immunotherapy

🕒 7 min

Most of us probably know someone who’s suffered from cancer, is still suffering or, unfortunately, we have it ourselves. Media daily feed us information on this topic, covering a wide range of news on the newest cancer drugs, treatments or medical discoveries. And yet, you might wonder why, after years and years of research, we still haven’t successfully found a universal cure for cancer. The answer to this is more complex than it seems – so let’s take it step by step.

THE ARMY INSIDE US

To understand cancer, we must first understand that it is a disease mounted against our immune system, and unique to each individual. But what is the immune system? Perhaps we can best describe it as a complex network of interacting cells and tissues that protect our body from infectious agents such as viruses or bacteria and malignant cells. It also removes cellular debris from our bodies. The bottom line is our immune system is a policeman and waste disposal.

The immune system spans many organs like the thymus, the spleen, and includes many kinds of cells and tissue, such as the lymph nodes, stem cells, T cells, B cells, Natural Killer cells etc.

To protect us, the immune system must distinguish a foreign agent – like viruses, bacteria, and malignant cells – from our own body and then effectively destroy it. It has developed mechanisms that effectively fulfill this role. So, here is the big question: why does our immune system ever fail to recognize that our body is developing cancer?

This very question is the basis of immunotherapy – a therapy approach that uses our immune cells to recognize cancer and destroy it.

A BODY INSIDE OUR BODY 

Cancer starts developing as a consequence of unrepaired mistakes during DNA replication in cells. This happens all the time, probably way more than you would actually think! Every time a cell in your body divides, about 120 000 mistakes are made! Luckily, your cells are very smart and manage to repair nearly all of those mistakes in every cell replication.

However, if the cells fail to repair important mistakes or immune system fails to destroy damaged cells, they can start to grow uncontrollably and can form cancer, a kind of tumor that can spread and become an independent entity in our body.

Cancer is an extremely heterogeneous disease. There are many different types of cancers and there is even more variation among cancers of the same type. What makes it difficult to treat is the fact that cancer develops from our own body, meaning it is unique to every individual.

Cancer behaves like a parasite. It develops when it successfully escapes immune system surveillance, builds its own system of food and oxygen supplies, along with a complex of supportive cells and proteins that protect it from ever getting detected and destroyed. So, cancer develops a way to block the immune system.

Only twenty years ago, Nobel laureate James Allison was one of the first people to realize that we can remove this blockade and activate the immune system to recognize and destroy cancer – something we call immunotherapy today.

CAR-T CELL THERAPY

There are several types of immunotherapy and deciding which one will be used depends on the type of cancer. To date, we can classify immunotherapy into five main types:

  • cell-based immunotherapies
  • immunomodulators
  • vaccines
  • antibody-based targeted therapies
  • oncolytic viruses

We won’t explain each type in details, but important to know is that they all work in different ways. Some help the immune system stop or slow the growth of cancer cells whilist others help the immune system to destroy cancer and stop it from spreading. They are often given in combination.

For exmaple, let’s start with cell-based immunotherapy.

Chimeric Antigen Receptor T cell therapy or CAR-T cell therapy for short, is one of the most rapidly emerging cell-based immunotherapies, shown to be particularly successful in hematologic (blood-related) cancer. This approach is based on T cells, which are taken from a patient’s blood and are subsequently genetically modified in the lab to intensify the natural immune response to cancer.

T cells play a critical role in orchestrating the killing of tumor cells. In CAR-T cell therapy, T cells are genetically engineered to produce receptors on their surface called chimeric antigen receptors, or CARs, using a disarmed virus. These receptors allow T cells to recognize and attach to proteins expressed on the surface of a tumor. After this, T cells can effectively kill the cancer cells. Once such T cells have been engineered, they are grown in the lab to produce millions of copies.

Finally, these cells are injected back into the patient. We can think of this as a “living drug” in the sense that the cells, once they are in the patient’s bloodstream, will find cancer, infiltrate it and start killing it. To make sure that the native immune system does not recognize the CAR-T cells as foreign and turn against them, patients are usually subjected to chemotherapy before immunotherapy.

PERSONALISED VACCINES

Most vaccines, like those against measles or tetanus, are preventive and meant to be injected into a healthy individual. This prepares the body to fight pathogens once it comes in contact with them.

However, personalized cancer vaccines are different. They are not designed to prevent the disease, but to help the body to defend against a tumor that is already present.

Often, cancer cells express proteins on their surface that are not present in healthy cells. These proteins are called antigens and are, in most cases, recognized by T cells. When the recognition of antigens fails, cancer can develop further. Personalized vaccines are designed based on the individual patient’s tumor antigens. They are composed of a pool of the individualized tumor antigens and adjuvants, substances that may help strengthen the immune response. Once injected back into the patient, the antigens will activate dendritic cells. Dendritic cells are very common in our immune system; they will engulf the antigen and present the it on their surface to induce a potent activation of tumor-specific T cells.
Personalized vaccines are often given in combination with other drugs like immune checkpoint inhibitors (ICI), which induce a stronger immune response. ICI are immunomodulators, one of five types of immunotherapy.

Immune checkpoints are a vital feature of healthy cells that prevents the immune system from attacking cells indiscriminately. They also play an important role in terminating the immune response after killing a pathogen.
However, the tumor can hijack this system and signal T cells to stop killing its cells. Immune checkpoint inhibitors are small molecules that will prevent the tumor from sending such inhibitory signals to T cells. Together with vaccines, they provide a potent way of tackling cancer.

Immune checkpoint inhibitors. Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body (left panel). Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells (right panel). Source: cancer.gov

In the end, it is worth mentioning the emergence of T-cell bispecific antibodies. Antibodies are proteins that are naturally produced by a type of immune cell called B cells to protect us from pathogens. In cancer research, scientists can produce customized antibodies against cancer cells. Once they bind cancer, they signal other cells to come and help in killing cancer cells. A new type of antibody-based immunotherapy called T-cell bispecific antibodies can target not only cancer cells but also T cells. This approach offers a more effective treatment option compared to previously developed cancer antibodies!

THE FUTURE OF IMMUNOTHERAPY 

It seems like immunotherapy represents a powerful way of battling cancer. However, even though breakthroughs are being made with many positive responses, it still isn’t widely used. How come?

Despite these advances, obstacles still exist.
One of the major challenges of immunotherapy is resistance to the treatment, as only a subset of patients shows a positive response to the therapy. The inability to predict treatment efficacy and patient response, as well as the high cost of treatment represent additional problems and require a lot of effort and many upcoming years of scientific research to fix.

Immunotherapy also has some side effects that can severely impact patient outcomes. They can vary from flu-like symptoms to more severe organ inflammation.

Nevertheless, these obstacles will likely be overcome by the implementation of novel drugs, more targeted cancer immunotherapies, and novel immonopreventive innovations that will reduce the cost of treatment and improve its efficacy. No doubt, treating cancer will largely depend on immunotherapy in the future, providing a successful weapon to battle cancer.


Want to read more about immunotherapy? Check the links below:

  1. A guide to cancer immunotherapy: from T cell basic science to clinical practice
  2. How T-Cells Protect You from Diseases
  3. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy
  4. Personalized vaccines for cancer immunotherapy

Did you like the article? Please tell us what you think in the comments section!

By Ivana Osredek

Ivana is a genetics student with a great interest in computational biology and big data analysis. She spends her free time doing trail running and preparing for a marathon.

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