CAR-T Therapy Challenges and Complication

Surgery, chemotherapy, radiation treatments, and targeted therapy have been the four pillars of cancer treatment for many years. Immunotherapy, however, is rapidly becoming the fifth pillar due to groundbreaking developments in CAR-T therapy. Immunotherapy involves using the patient’s own immune system to destroy cancer cells. The immunotherapy sub-branch of CAR T-cell therapy has been showing promising signs of improvement in cancer treatment and outcomes in recent years.

What Is CAR-T Therapy?

Chimeric antigen receptor T-cell therapy (CAR-T) therapy is a kind of adoptive cell therapy. Doctors collect immune system T-cells from a patient and then genetically modify those cells. The T-cells are equipped with new receptors that can specifically identify cancer cells, and then instruct the immune system to destroy those cells. CAR-T therapy basically reprograms a patient’s immune system, so that it will find and kill cancer cells. T-cells can also be harvested from a matching donor to be used for the therapy, although patient-derived therapies are the most common.

How Does CAR-T Therapy Work?

Blood is initially drawn from a cancer patient and then the T-cells are separated. The T-cells are then genetically altered in a laboratory setting. Once they’re altered, the T-cells develop chimeric antigen receptors that can recognize and attack cancer cells. Once some initial CAR-T cells are created, millions of new cells that are a genetic match for the patient are grown in the lab. Those cells are then infused back into the patient in the process called CAR-T therapy or CAR T-cell therapy.

What Can CAR-T Therapy Treat?

CAR-T therapy treatments have only been approved for several different types of cancer since 2017, although clinical trials started years earlier. It’s approved for children with Acute Lymphoblastic Leukemia (ALL) and for adults with Diffuse Large B-Cell Lymphoma. CAR-T therapy for these two types of cancer has met with amazing success, resulting in an 83 percent overall patient response.

CAR-T therapy was also approved by the FDA in 2020 for the treatment of adults with mantle cell lymphoma (MCL). This was a rapid approval by the FDA, since clinical trials of CAR-T therapy have proven to be remarkably safe in most cases. CAR-T therapy is also going through clinical trials for some non-cancer illnesses, like diabetes and fibrotic liver disease.

Challenges & Complications of CAR-T Therapy

The success of CAR-T therapy treatments has led the FDA to approve these treatments, but challenges still exist. T-cell exhaustion, in which T-cells can become dysfunctional as a result of cancer, is still a problem researchers are working to overcome. T-cell proliferation is another complication. In this problem, T-cells attract cytokines that then recruit cytotoxic T-cells, B cells and other potentially harmful cell types that can lead to inflammation.

Another challenge is the fact that the T-cells used for treatment must be from the individual cancer patient or a genetic match. There is no way to mass produce T-cells at this point in time, which could then be distributed widely for potential use in all patients. It may happen in the future, but for now, manufacturing clinical-grade cell therapies on a large scale is impossible.

T-cell processing and reengineering is currently done manually. This presents two last major problems: The process takes a lot of time, and it costs a tremendous amount of money. The large-scale production of CAR T-cells is therefore cost-prohibitive. And excess time for the production of these cell therapies is something many cancer patients simply do not have.

Deno Max
the authorDeno Max