Immunotherapy: Engineering the Immune System to Tackle Fatal Diseases

The immune system is a collection of organs, cells and substances in the body that help protect you from infections and other diseases. The immune system tracks substances inside the body, and when a foreign substance is detected, it sets off an alarm and attempts to get rid of it. When the immune system gets hit with cancer cells, it doesn’t always recognize the cell as foreign because the cells aren’t much different from normal cells. Consequently, fatal cells like cancer cells are allowed to take over the body (Cancer Organization).

In cancer, the immune system is often deregulated and lacks the ability to remove the tumour cells. However, advances in medical technology have enabled scientists to control the work of certain immune cells – these therapies are termed ‘immunotherapies’. Immunotherapy, therefore, is a form of treatment that triggers the body’s immune system to work harder and smarter at getting rid of the cancer cells. There are two ways this can be done: first, by boosting the immune system, and second, by training the immune system to specifically fight cancer cells (Cancer Organization).

There are different types of immunotherapy treatments available. Monoclonal antibodies are replicated immune system proteins that attack a specific part of a cancer cell. Cell-based immunotherapies happens when the immune system detects a foreign cell (CAR T-cell) and attacks it. These cells are engineered in the laboratory; thus, they may also be called cell therapy or adoptive cell transfer therapy (Cancer Organization).

Cancer cells find ways to not be detected as “foreign”, and the immune system does not get alerted when these cells start infecting the body. Immune checkpoints are drugs that target these “checkpoints”, or molecules on certain immune cells that need to be activated or inactivated to start the immune response. When the cell to cell communication needs to be enhanced, cytokines are added to enhance the faster spread of immune signaling in a more efficient manner (NCBI).

Cancer vaccines are another form of biological response modifiers. They work similarly to traditional vaccines taken for infectious diseases and work by helping the immune system fight infections and diseases. There are different types of cancer vaccines available:

  • Tumor Cell Vaccines: This type of vaccine is produced by isolating the tumor cells and then administered to the individual from where to tumor cells were isolated. This typically results in tumor cell death (NIH).
  • Antigen Vaccines: These are vaccines made of only one or a few antigens, rather than whole tumor cells to boost the immune system. The antigens are usually proteins called peptides.
  • Dendritic Cell Vaccines: Dendritic cells are special immune cells that helps the immune system recognize cancer cells. They break down the cancer cells (including antigens), and let the immune cells recognize them. The T cells attack the cancer cells and help the immune system get back on track (American Cancer Society). This type of vaccine has been the most successful. Dendritic cells are not usually present in large quantities to allow for a quick immune response, thus, dendritic cell therapy involves laboratory processed cells which are given to a patient in order to increase dendritic cell count in the patient’s body.
  • Vector-Based Vaccines: Vectors are altered viruses, bacteria, cells or other structures that are used to get the antigens into the body. The alterations allow them to enter the body safely and can no longer cause diseases.

The different diseases immunotherapy treats

Immunotherapy has been used or researched for the purpose of treating a variety of diseases, but mostly the two main classes: autoimmune diseases and cancer. At the vanguard of research and development of therapies for autoimmunity and cancer are immunotherapies. Studies have found that the more the immune system is manipulated to treat autoimmunity or cancer, the better the immune system gets at regulating self-tolerance and resisting microbes. The holy grail of therapies for these diseases is to reprogramme the immune system and maintain homeostasis without the need for continuous treatment. Conventional therapies still require a wide array of suppressive regimens with prolonged chemotherapy for cancer treatment causing quite serious side effects (NCBI).

Before doctors and researchers can find out how to maintain homeostasis from immunotherapy, they need to solve other parts to the puzzle. Doctors are finding it difficult to predict the patient’s wellbeing after immunotherapy treatment. The results are inconsistent when the treatment is used on patients with similar genetic make-ups and cancer types. So far, results have been outstanding for some patients; however, for others, the results have been far less impressive (NCBI).

The involvement in research spans from the early stages of discovery in the laboratory, right through to clinical trials for patients. There is also more focus on personalizing treatment, thus greater collaboration is needed to capture and compare data.

What are the challenges to having immunotherapy as a routine treatment

Immunotherapy is one of the main foci of cancer researchers, and has the potential to be quickly incorporated as a standard-of-care treatment for some types of cancer in some countries, for example, the US where commercial insurers or patients are more likely to be able to pay the hefty prices for these drugs. However, to fully harness the value of immunotherapy, there needs to be increased research and technology to help identify additional biomarkers and cancer pathways, tumor heterogeneity, variability in cancer type and stage, treatment history, and the underlying immunosuppressive biology of cancer (NCBI).

For the opportunity of a second chance in life, the price of immunotherapy has been shocking for many. The pricing which is beyond $50,000.00 is still too expensive to be used routinely by a) people with insufficient medical coverage in western countries with insurance e.g. US , b) not sufficiently value-add in countries with socialised healthcare eg UK or Sweden and c) far too expensive for countries like the Philippines for both those paying out of pocket or via insurance.

Patients still have a chance on relapsing, and needing a dose of the treatment more than once. In addition, patients still need to pay more for pre-infusion treatment costs, drug administration and hospitalization costs, and other costs related to follow-up care (ONC Live).

Drug companies claim that the cost for these drugs are conservative, and they could have charged a lot more than what they are currently charging. According to Novartis, American taxpayers invested roughly $200m into “foundational” research on CAR-T cells therapies (The Guardian).

Although the approval of gene therapies by the FDA (Food & Drug Association) in the U.S. for the treatment of cancer and other diseases, the procedures and treatment still need to go through hefty risk evaluations and mitigation strategies. The side effects of these treatments for some patients can be deadly for some patients when the vital organs are attacked by the modified T cells that are reintroduced into the body (The Independent). A proper certification needs to be put in place for staff involved in prescribing, dispensing, and administering these treatments.

For patients to be fully cleared off cancer or other fatal diseases through immunotherapy, most patients still need to go through a trial and error procedure until they get to regression or remission.

The future of immunotherapy

One of the strategies for better efficiency in treatment will come through multiple clinical trials over the next several years. Clinical trials are critical to bringing new treatments to more patients with more types of cancer.

There are opportunities for patients to participate in clinical trials. At the moment, only 3% to 6% of cancer patients who are eligible for clinical trials participate (Cancer Research Institute).

The advances in immunotherapy are the result of long-term investments in research. More research and more clinical trials need to be done to answer the common questions surrounding immunotherapy such as: why immunotherapy is effective in some patients and not in others; which combination of different cancer treatments are most effective to patients; how to improve the safety of the therapy; and, how to cure cancer and other fatal diseases in the most effective and economical way.

There is still a lot of work to be done to establish immunotherapy as a standard of care for all tumors, to broaden the applicability across a variety of cancers, and to enhance its efficacy for a wider range of patients. In the future, immunotherapy treatment will have a more targeted approach that enhances efficacy and reduces toxicity. To achieve this, more research on the integration of conventional immunological approaches needs to be done with the support of pharmaceuticals, the government, research organizations, and patients. More funding also needs to be infused into the research to help expedite the process, and at the same time, help cancer patients sooner.

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