The recent successes of CAR-T therapy for cancer patients have scientists “dreaming big” when it comes to the future of these novel treatments. Chimeric antigen receptor T-cells are genetically altered from a patient’s own immune system, and are designed to target and destroy cancer cells. There are some drawbacks to the therapy, however.
CAR-T therapy has successfully treated leukemia and lymphomas, but the cancers often come back. The T-cells can also trigger a storm of cytokines in patients, which can be life-threatening. It will take time to overcome the challenges of CAR-T therapy, but scientists are hopeful that the issues will be resolved and then they’ll move on to bigger and better immunotherapies with altered T-cells.
Controlling CAR T-Cells
CAR-T therapy reprograms the patient’s T-cells to identify cells with specific targets and destroy them. This works greatly against cancer cells, but the altered T-cells will kill any cell that they recognize with the same receptors as cancer cells. And there’s currently no way to turn these T-cells “off” once they are inside the patient’s body.
Synthetic biologists are hoping to develop “controllable CARS” eventually, which can be turned on or off using various methods. This would prevent the T-cells from running wild in the patient’s system long after they’ve done their work on cancer cells or tumors. One team of researchers is working to engineer T-cells with a protein switch that turns on in the presence of blue light, and turns back off when the light is no longer applied. Another method being attempted is to switch the T-cells on in the presence of ultrasound radiation.
Biomolecular Computer CARs
Cancer cells and healthy cells cannot be identified by one simple marker. Unfortunately, that’s what CAR T-cells currently do: They target a specific marker and kill the associated cell, whether it’s a cancer cell or a healthy cell.
Researchers working in this area hope to be able to create CAR T-cells that can make simple logical decisions, so that they’ll only target cancer cells. If CAR T-cells can be reprogrammed to identify multiple proteins in a cancer cell, and only attack those cells, it would eliminate the problem of healthy cells being killed. This method is know as logic-gating the T-cells, or basically turning them into an entity that operates similar to a very simple computer program.
Stronger Armor for CAR T-Cells
Under current CAR-T therapy, the T-cells can stop working eventually. Solid tumors sometimes have the ability to fight off immune system attacks, which exhausts the CAR-T cells until they “give up the fight.” This can allow cancers to resurface.
The microenvironment around a solid tumor is highly toxic to CAR T-cells, therefore. Scientists are hoping to create an armored T-cell that is more likely to survive in that microenvironment, while effectively defeating cancer.
In layman’s terms, CAR T-cells become exhausted and quit over time. Researchers at Stanford University have managed to create a CAR T-cell that “takes breaks” between bouts of fighting solid tumors. It seems that giving these T-cells a rest can help them to last longer before reaching cell exhaustion.
New Types of Cells?
CAR-T therapy is one of the most promising advancements in cancer treatment in recent decades. However, there may come a time when genetic science leads doctors to abandon altered T-cells completely. Some researchers are working on new laboratory-created cancer-fighting cells that do not occur in nature.
As one example, a company called CoImmune is using a synthetic cell called a cytokine-induced killer (CIK) cell, and attaching CAR cells to it. Completely artificial cells like this could eventually lead to an effective cancer treatment that leaves behind the challenges of CAR-T therapy. Scientists are still a long way from achieving that, though.