How does immunotherapy against cancer work?

Part 1: immunotherapy based on adoptive immune cell transfer

Diana Campillo Davó · 15-10-2020 10:00 · CEBE answers

The immune system consists of a complex group of tissues, organs, proteins, and cells—called leucocytes or white blood cells—in charge of the protection of our body against foreign agents such as viruses and bacteria, but also against tumor cells. However, this defense mechanism may fail, leading to cancer.

Immunotherapy is based on the use and improvement of our immune system for therapeutic purposes. When it comes to cancer, immunotherapy has three main objectives, (1) preventing the formation of tumors, (2) training the immune system to fight cancer, or (3) directly targeting tumor cells. Therefore, immunotherapies can be based on tumor protein vaccines, and vaccines against tumor-causing viruses (Objectives 1 and 2); on immunomodulators to promote immune responses to cancer (Objective 2); on antibodies against tumor antigens, or to activate the immune system (Objectives 2 and 3); on the adoptive transfer of cells of the immune system (Objective 3), and on viruses capable of destroying tumors (Objective 3).

In this blog entry, I explain how to attack tumors using adoptive immune system cell transfer.

In the immune system, there are cells such as T lymphocytes (or T cells) and natural killer cells (NK cells) capable of detecting and killing tumor cells. Whenever the number of T cells and NK cells are low, or should they not function properly (especially in cancer patients), or in case we want to improve their antitumor activity, an adoptive transfer of these cells is to be performed. In the event that these cells are present in the patient, they should be isolated, expanded in the laboratory, and infused back into the patient in order to improve their antitumor response. Otherwise, were these T cells and NK cells undetectable, or should they be unable to naturally recognize tumor cells, normal T cells and NK cells from the patient or a compatible donor should be isolated, multiplied, genetically modified to recognize the tumor, and infused back into the patient. These genetic modifications mainly focus on the production of receptors, that is, of proteins capable of recognizing parts of the malignant cells. These receptors act as a key that unlocks a specific lock in the tumor. This lock is made up by tumor antigens, or in other words, components of tumor cells that promote an immune response. The two main categories of receptors used in this kind of therapy are T-cell receptors (TCR), naturally produced by the said cells, and chimeric antigen receptors (CAR), a hybrid of antibody and T-cell receptor. Once expanded and/or genetically modified, T lymphocytes and NK cells will be infused into the patient, so they can patrol the body in search of tumoral cells. When detected, T cells and NK cells will attack the tumor cells, causing them to die.

Many investigators are currently relying on this kind of therapy. Consequently, they study the potential use of several types of immune cells, develop receptors targeting new tumor antigens, and strive to improve their strength and specificity. Likewise, they conduct multiple clinical trials in order to ensure their safety. It is the great progress made in this field over the last years that has recently made it possible for adoptive transfer-based treatments to have been cleared for marketing, thus increasing the number of therapies available to cancer patients.


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