T-cells are often called the workhorses of the immune system because of their critical role in the body’s fight against pathogens. These are a subdivision of white blood cells which help the immune system in killing viruses, bacteria, and cancer cells.
For years, the foundations of cancer treatment were chemotherapy, surgery, and radiation therapy. However, recently, therapies that boost the power of a patient’s immune system to attack tumors has emerged as a new pillar in the field. The most advanced of them, so far, is the CAR T-cell therapy. Find out what role the T-cells play and what they mean for the future of cancer treatment.
Types of T-Cells
Before looking into the function of T-cells in cancer, get to know their different types and abilities.
- Regulatory T-cells – These are believed to suppress the immune system so that it doesn’t affect areas that are not within its normal scope (as it does in autoimmune diseases). It’s important to note, however, that central aspects of their biology remain shrouded in mystery and continue to be deliberated.
- Helper T-cells – These employ other immune cells and create an immune response.
- Cytotoxic T-cells – These cells look for and directly assault foreign invaders such as viruses, bacteria, and cancer cells.
- Memory T-cells – These are responsible for remembering details on the surface of viruses, bacteria, or cancer cells that they have encountered before.
- Natural Killer T-cells – Also known as NKT, natural killer T-cells respond to the presence of tumor cells. They are not the same thing as natural killer cells, although they do have similarities. Both are subsets of lymphocytes that share common ground. They also participate in anti-tumor immune responses together. However, NKT cells are cytotoxic T-cells that need to be pre-activated before they do their work.
The bone marrow produces the T-cells, which will then mature and develop in an organ in the chest called the thymus. This is the reason they are called T-cells, which stands for thymus-derived cells. Once they mature, T-cells travel in the blood and also stay in lymph nodes.
Function in Cancer
It can be confusing to talk about T-cells, but their function in our fight against cancer is invaluable. The first step in getting rid of the disease, the cells have to “see” it first. They work in both indirect and direct ways to combat tumor cells. Helper T-cells naturally organize and orchestrate their battle against the disease. Killer T-cells, on the other hand, have a more direct approach to finding cancer cells. They can also be stimulated to kill the invaders.
Ways Cancer Affects T-Cells
In cancers like T-cell lymphoma, the T-cells themselves become malignant. Cancer can also take over the bone marrow. Lymphomas and other cancers can spread to the area and crowd out healthy stem cells, leading to the depletion of T-cells. Similarly, chemotherapy can directly destroy T-cells and other white blood cells.
Adaptative T-cell transfer is a rapidly emerging immunotherapy approach that makes use of the patient’s own immune cells to attack the cancer. There are three different methods to adoptive T-cell transfer:
- T-cells are collected from the body and genetically engineered to fight antigens on cancer cells
- T-cells are taken out from a sample of a patient’s tumor and grown in a laboratory
- Scientists equip the collected T-cells with special receptors known as chimeric antigen receptors (CARs). When transferred back to the patient, these CAR T-cells identify and fight malignant cells.
There are different types of immunotherapy treatments under this adaptive T-cell transfer, like endogenous T-cell therapy and tumor-infiltrating lymphocytes, but only CAR T-cell therapy has advanced the furthest in clinical development.
CAR T-Cell Therapy
Dr. Renier Brentjens of the Memorial Sloan Kettering Cancer Center in New York and an early leader in the CAR T-cell field explains that CAR T-cells is similar to giving patients a living drug. The therapy requires drawing blood from patients and separating out the T-cells. Then, with a disarmed virus, the collected cells are modified genetically to manufacture receptors on their surface.
These receptors are synthetic molecules that allow the T-cells to recognize and attach to an antigen on tumor cells. The engineered T-cells are then sent to the lab to be expanded into the hundreds of millions. The last step is the infusion of the CAR T-cells into the patient. If all goes as planned, the modified cells further multiple in the patient’s body and, with direction from their receptor, identify and kill cancer cells that harbor the antigen on their surfaces.
Until recently, the use of this treatment has been restricted to small clinical trials, mostly in patients with advanced blood cancers. So far, the therapy is only approved to treat two groups of people with certain types of cancer:
- Kids and young adults up to age 25 with precursor B-cell acute lymphoblastic leukemia that hasn’t gotten better with treatment or that has relapsed after initial recovery.
- Adults with aggressive large B-cell lymphoma that hasn’t improved with therapy or when there is a recurrence of the disease.
Most of these patients have few, if any, effective treatment options available. Dr. David Porter, director of blood and marrow transplantation at the Hospital of the University of Pennsylvania says that you have to have failed two prior therapies to be a candidate for CAR T-cell.
Evolution of CAR T-Cell Therapies
Other reconfigurations or refinements of CAR T-cells are being tested. One solution is the development of CAR T-cell treatments that utilize immune cells taken not from patients, but from healthy donors. The objective is to create a so-called off-the-shelf therapies that are immediately available for use and don’t have to be produced for each patient.
T-cells can be taught to recognize tumor cells and kill them. Scientists continue to investigate these cells to find out how to reach their maximum potential. With the development of CAR T-cell therapies, patients who are not having an optimal response to chemotherapy or other treatments can still hope to recover. In the next few years, there could be dramatic progress that will push the boundaries of what many people thought was possible with these adoptive cell transfer-based therapies.