Immunotherapy and Cellular Therapies

Immunotherapy and Cellular Therapies

What is immunotherapy?

Immunotherapy is a type of treatment that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Some types of immunotherapy target only certain cells of the immune system. Others affect the immune system in a general way. Types of immunotherapy include cytokines, vaccines, Basil Calmette-Guerin (BCG), and immune checkpoint inhibitors in the form of monoclonal antibodies.

Is immunotherapy a targeted therapy?

Targeted cancer drugs are drugs of mostly small molecule structures designed to target specific genetic changes, such as mutations associated with cancer. For this reason, immunotherapies and targeted drugs are different from each other. While the purpose of immunotherapies is to activate the immune system against cancer, targeted drugs aim to suppress genetic changes that trigger cancer.

Immune Checkpoint Inhibitors

A new type of immunotherapy called immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment and has contributed to the lives of millions of patients worldwide in 10 years. The discovery of immune checkpoints was awarded the 2018 Nobel Prize in Physiology or Medicine. When it comes to immunotherapy in cancer, immune checkpoint inhibitors come to mind.

The immune system is normally capable of finding and destroying damaged and foreign cells. However, one of the 10 Hallmarks of Cancer is that cancer cells develop some ways to protect themselves from immune system attacks. Our normal cells carry some molecules on their surfaces to protect them from immune system attacks. The warrior T cells of the immune system do not recognize these molecules and attack normal cells. Cancer cells also appear as false friends to T cells by carrying these molecules. Thus, they evade the immune system. In the 1990s, Dr Allison discovered the first of these molecules (CTLA-4). Allison also demonstrated its anti-cancer effect in mouse models by designing inhibitors that target this protein. Independent of Alison, Japanese scientist Tasuku Honjo discovered the second checkpoint molecule (PD-1) in 1992. Of these checkpoints, CTLA4 is likened to a car's handbrake, and PD-1 to a, and drugs in the form of monoclonal antibodies developed against them are immune checkpoint inhibitors.

What are the side effects of immunotherapy?

It is not true that immunotherapies do not have side effects. While these drugs cause fewer side effects than chemotherapies, they can cause serious side effects – most of them mild – due to overactivation of the immune system.

The general characteristics of immunotherapy side effects are as follows:

  • Immunotherapy side effects occur when the immune system, which is activated against cancer, also damages normal parts of the body.
  • In general, frequency of side effects and severity of monoclonal antibody type of immunotherapies.
  • Combination immunotherapies have more frequent and severe side effects than single agent (monotherapy) immunotherapies.
  • Immunotherapy side effects can affect almost all organ systems. Most commonly skin, intestine, endocrine (hormonal system) and lungs; more rarely cardiovascular system, bone marrow, kidney, nervous system and eye.
  • Mild side effects usually occur during treatment with immunotherapies, but unlike chemotherapies, these side effects can sometimes last for months.
  • The most common immunotherapy side effects are mouth sores (mucositis), diarrhea, skin allergies, and flu-like complaints (such as fatigue, fever, chills, weakness, nausea, vomiting, and rash).

How long does immunotherapy treatment take?

İmmune checkpoint inhibitors are commonly used in cancer. They are of monoclonal antibody structure and are administered intravenously in the form of serum. The application time in each cycle is between 30-60 minutes. Immunotherapies are administered every 14 or 21 days, depending on the drug used. Total immunotherapy treatment duration is as long as the patient continues to respond to treatment; In general, immunotherapies are administered for up to 2 years. In case of intolerable side effects or progression of the cancer, the treatment is discontinued.

Cellular therapies

Today, there are many different methods and drugs used for cancer immunotherapy; cellular immunotherapy is one of them.

Tumor-infiltrating lymphocytes

The purpose of adaptive T cell transfer is to get the patient's own T cells to fight cancer. For this purpose, T cells are isolated from the patient and activated against cancer cells by applying genetic techniques. These modified cells are then returned to the patient. It is aimed to activate the immune system.

CAR T-cells

Yet another new strategy is chimeric antigen receptor (CAR) T-cell therapy. In this treatment, the T cells in the patient are collected and reprogrammed in the laboratory environment and re-inoculated into the patient. Reprogrammed T cells produce certain proteins that easily find and attack cancer cells in the body. Initial results are that various difficult-to-treat blood cancers (leukemia) may benefit from CAR-T cell therapy. For example: CAR-T cells for CD-19 are programmed to attack malignant B cells that have CD19 molecules on their surface.

It is thought that CAR T-cell therapy will be used more extensively in the future. In addition, there are studies in which not only T-cells, but also NK and macrophages are tested for this purpose.