29 September 2022
To mark blood cancer awareness month, Dr Rachel Perret talks about how immunotherapies show promise as a future standard of treatment for blood cancer.
Our blood is like a network of interlinking rivers and streams that transports nutrients, oxygen and different types of cells from one part of our body to another. Blood cancer can disrupt this carefully balanced system. Here at the Malaghan Institute, one of our main research areas is developing immunotherapies to target cancer.
“Immunotherapies like CAR T-cell therapy and antibody-therapies are particularly well suited to treating blood cancers, as the immune cells and proteins naturally circulate through the blood and lymphatic system where blood cancer is found,” says Dr Rachel Perret, Team Leader of the Freemasons CAR T-cell Research Programme at the Malaghan Institute.
The blood itself contains several different types of immune cells to protect us from threats. Blood cancer occurs when mutations develop in one cell in this vast network, effectively contaminating the rivers and streams. This mutated, dysfunctional cell starts to divide uncontrollably, in some instances the cancer cells crowd out healthy cells preventing them from carrying out their important functions.
CAR T-cells are modified versions of immune cells called T-cells which already have the power to destroy individual diseased or damaged cells. During the modification process, these T-cells are equipped with instructions on how to identify a specific type of cancer cell so that they can target and kill them. The CAR T-cells are then released into the body to decontaminate the bloodstream from cancer cells.
“It’s pretty amazing that a single IV injection of CAR T-cells can replace months or years of chemotherapy and radiation treatments.”
Cancer cells are often very deceptive and are careful not to show obvious signs of their malignancy on the outside of the cell. This allows them to continue to circulate and divide rapidly in the blood stream without raising alarm with the body’s immune system.
This means it can be difficult to pinpoint exactly what the CAR T-cells should be looking out for to identify the cancer cells. If they are programmed to identify proteins that are present more widely than in the cancer cells, then they can wipe out other, healthy cells in the body and have widespread adverse effects. If the target is too narrow, all the cancer cells may not be destroyed, and the cancer may come back.
To balance this problem, these CAR T-cells are usually programmed to wipe out the specific population of immune cells that the cancer is present in. For example, the T-cells at the Malaghan Institute are being programmed to target B-cell lymphoma. This means that normal B-cells, as well as the lymphoma cells, will be eradicated. Then patients will receive blood transfusions to provide antibodies that will maintain the original immune function of the missing B-cells.
Dr Perret’s team are working on a number of projects to make CAR T-cells more effective including research to develop:
- dual CAR T-cells that can target two different proteins to pin down the cancer cells further.
- CAR T-cells that can treat solid tumours where the cancer cells form a tight clump of cells rather than circulating in the blood stream.
- safer CAR T-cells by implementing a “kill switch” that can turn them off if needed.
“CAR T-cells have revolutionised the way we treat certain blood cancers, with some patients reporting that they can feel tumours in their lymph nodes melting away within days. It’s pretty amazing that a single IV injection of CAR T-cells can replace months or years of chemotherapy and radiation treatments,” says Dr Perret.
“The road to further improving this therapy, making it safer and also applicable to other cancer types, is a long and challenging one, but we’re excited and hopeful that we will soon have the right CARs we need to drive to the finish line.”