A cancer cell (white) being attacked by immune cells (red).
Picture: National Institute of Health.
Immunotherapy is creating a revolution in the treatment of cancer. By inducing the immune system to attack cancer cells, cancer doctors have a powerful extra tool at their disposal to fight 'the king of all maladies' called cancer.
Immunotherapy consists of several methods that spur on white blood cells to attack cancer cells. This can be done by checkpoint inhibitors, dendritic cell therapy and chimeric antigen receptor T cell therapy.
Immunotherapy consists of several methods that spur on white blood cells to attack cancer cells. This can be done by checkpoint inhibitors, dendritic cell therapy and chimeric antigen receptor T cell therapy.
Checkpoint inhibitors
Checkpoint inhibitors target the brakes that cancer cells put on the immune system. Tumor cells express proteins on their surface that make contact with white blood cells (T-cells) to dampen them down. The white blood cells can't destroy the tumor cells anymore. Checkpoint inhibitors are substances (antibodies) that latch onto specific proteins ('checkpoint detector proteins', like CTLA-4 or PD-L1) on the white blood cells that cancer cells normally target to deactivate the white blood cells. This enables the white blood cells to kill the cancer cells, with some impressive results. Certain checkpoint inhibitors can eliminate advanced skin tumors in one in five patients. That's encouraging because advanced skin cancer is very difficult to treat. Scientists are experimenting with combining different checkpoint inhibitors. Examples of some checkpoint inhibitors are:
- ipilimumab (Bristol-Myers Squibb): lung cancer and melanoma (clinical trials for use in other cancers are going on)
- nivolumab (Bristol-Myers Squibb): lung cancer, other cancers (clinical trials for use in other cancers are going on)
- pembrolizumab (Merck): melanoma (initially), lung cancer, other cancers (clinical trials for use in other cancers are going on)
- avelumab (Merck KGaA, Pfizer): lung cancer, other cancers (clinical trials for use in other cancers are going on)
- durvalumab (AstraZeneca/MedImmune): lung cancer, other cancers (clinical trials for use in other cancers are going on))
- tremelimumab (AstraZeneca/MedImmune): lung cancer (clinical trials for use in other cancers are going on)
- atezolizumab (Genentech/Roche): lung cancer, bladder cancer, other cancers (clinical trials for use in other cancers are going on)
Dendritic cell vaccines
Dendritic cells are immune cells that are spread across the body. They capture pieces of tumors (tumor antigens) and present them on their surface, enabling white blood cells to make contact with these tumor antigens, allowing the white blood cells to learn to recognize the tumor antigens. In this way, the white blood cells can attack the whole tumor. Dendritic cell vaccine therapy consists of imitating this process in the lab: dendritic cells are extracted from the body, put in a test tube together with tumor antigens. The dendritic cells then express these tumor antigens on their surface. The dendritic cells are re-injected into the human body, where white blood cells (T helper cells and cytotoxic T cells) learn to recognize these tumor antigens so that they can attack the tumor in the body.
Chimeric antigen receptor T cell (CAR-T cell) therapy
White blood cells (T cells) use antigen receptors (proteins that stick out of their surface as hooks to latch onto cancer cells) to attack and destroy cancer cells. CAR-T cell therapy consists of extracting white blood cells (T cells) from patients, infecting them with a virus that carries a chimeric antigen receptor (a powerful antigen receptor) resulting in the antigen receptor being expressed on the surface of the white blood cells. These cells are injected back into the body. With their powerful chimeric antigen receptor, they can seek out and destroy cancer cells. This therapy works especially well for liquid tumors, like leukemias and lymphomas. This therapy can destroy cancer in up to 90% of patients with aggressive leukemia. However, CAR therapy is very powerful and patients run the risk of succumbing to an overactivated immune system attacking the cancer, also called an 'immune storm'.
Even more promising therapies on the horizon?
These immunotherapy therapies have much potential. However, a new technology called CRISPR-cas 9 could be even more promising for treating cancer, since it can combine several of the immune methods described above.
Scientists can use CRISPR-cas 9 to rewrite the DNA of white blood cells so that these modified white blood cells don't express checkpoint detector proteins (making them unable to be deactivated by cancer cells) and are equipped with chimeric antigen receptors that recognize tumor pieces (tumor antigens).
This would make these white blood cells very powerful to destroy cancer cells. Perhaps too powerful. There is the risk that these modified cells could unrestrainedly attack non-tumor tissue, like the gut or adrenal glands, precipitating an auto-immune reaction. However, studies with animals and humans show that these side effects can be mitigated or avoided.
Author: Dr. Kris Verburgh
Scientists can use CRISPR-cas 9 to rewrite the DNA of white blood cells so that these modified white blood cells don't express checkpoint detector proteins (making them unable to be deactivated by cancer cells) and are equipped with chimeric antigen receptors that recognize tumor pieces (tumor antigens).
This would make these white blood cells very powerful to destroy cancer cells. Perhaps too powerful. There is the risk that these modified cells could unrestrainedly attack non-tumor tissue, like the gut or adrenal glands, precipitating an auto-immune reaction. However, studies with animals and humans show that these side effects can be mitigated or avoided.
Author: Dr. Kris Verburgh
RSS Feed