CAR-T Therapy: When medical breakthroughs bear steep price tags

In 2010, five-year-old Emily Whitehead was diagnosed with acute lymphoblastic leukemia (ALL), a type of cancer that affects white blood cells. After years of intense chemotherapy, bone marrow transplants, and repeated relapses that seemed to defeat all hopes for remission, Emily’s parents brought her to the Children’s Hospital of Philadelphia in a final effort to find a successful treatment. There, a clinical trial was underway to antigen receptor (CAR)-T therapy, a novel cancer treatment that was largely unheard of at the time. In 2012, Emily became the first pediatric patient to receive this therapy – and thirteen years later, she remains cancer-free and lives a normal teenage life.

Emily’s recovery sparked global interest in CAR-T therapy and demonstrated its potential to treat otherwise incurable cancers. Since then, thousands have benefitted from this treatment. As of 2019, five CAR-T therapies have been authorized in Canada for the treatment of various blood cancers, including certain types of leukemia, lymphoma, and multiple myeloma.

However, implementation of CAR-T therapy remains challenging from logistical and financial perspectives, especially when considering a single infusion for a patient can cost roughly $400,00 to $500,00 CAD. This article explores the science behind CAR-T therapy, the extensive manufacturing process that contributes to its high cost, and potential strategies that may render CAR-T therapy more accessible and affordable for all.

What are CAR-T cells and how are they made?

As its name suggests, CAR-T therapy is based on a type of immune cell known as the T cell. These cells play an important role in detecting abnormal or unhealthy cells, including cancer cells, in our body. CAR-T therapy harnesses this natural function of T cells but provides them with an extra “boost,” allowing them to become more potent and effective cancer cell killers.

The development of CAR-T therapy begins with isolating T cells from the blood of a cancer patient: a process called apheresis. These cells are then genetically engineered to express chimeric antigen receptors (CARs): synthetic proteins located on the surface of T cells that enable them to specifically recognize cancer cells. The modified cells are further expanded in the lab to produce millions of CAR-T cells, which are reinfused back into the patient. Once infused, CAR-T cells can circulate throughout the body and attack tumour cells. CAR-T cells can also persist for years after the initial infusions, remaining armed for attack if the cancer attempts to re-emerge.

Challenges of current manufacturing practices

CAR-T therapy is unique because it must be manufactured on a patient-specific basis. Each patient’s T cells must be individually harvested and modified in specialized facilities, which requires highly skilled labor and quality control to ensure safe manufacturing processes. In Ontario, four healthcare centers currently offer CAR-T treatment. Once apheresis is completed at one of these centers, the cells are shipped to the United States for CAR manufacturing– a process that can take weeks to months before the final CAR-T product is ready to be infused back into the patient. Following the treatment, patients must be closely monitored for serious side effects such cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (iCANS). These complications can occur when the immune system goes into overdrive, causing the release in an overload of inflammatory proteins called cytokines. CRS may present symptoms including fever, fatigue, and shortness of breath. iCANS occurs when these cytokines cross the blood–brain barrier and enter the cerebrospinal fluid, causing neurologic symptoms such as tremors, confusion, and in severe cases, seizures. Both CRS and iCANS can be fatal if not managed appropriately.

Altogether, not only is CAR-T cell manufacturing time-intensive, expensive, and resource-heavy, but the frequent follow-up appointments required to monitor these side effects further add to the overall burden on both patients and the healthcare system.

The path forward

As CAR-T therapy gains traction in the oncology field, the next challenge is expanding its reach and accessibility. Currently, CAR-T manufacturing follows a centralized model, in which pharmaceutical companies operate one major production facility in North America and another in the European Union.  While centralized manufacturing helps maintain consistent product quality, it increases production time, reduces customer capacity, and drives up overall costs. An alternate strategy is a decentralized, “point-of-care” model, which involves producing CAR-T cells at or near the location where patients receive treatment. Once established, this approach could dramatically reduce wait times, simplify logistics, and lower expenses. In Canada, the Canadian-Led Immunotherapies in Cancer program is actively investigating ways to build domestic manufacturing capacity, paving the way for “made-in-Canada” CAR-T therapies that are both faster and more affordable.

Developing “off-the-shelf” cell therapies may be another viable solution. This involves engineering T cells isolated from a single donor, using them to treat multiple patients at a time. Traditional CAR-T therapy is currently limited by the need to use the patient’s own T cells, which is essential to avoid the dangerous immune reactions that can arise from introducing foreign donor cells. Thus, an ongoing area of research focuses on modifying CAR-T cells to make them safe for transfer between unrelated individuals. Scientists are also exploring the option of developing CAR therapies with other immune cell types, such as Natural Killer (NK) cells and invariant Natural Killer T (iNKT) cells. Similar to T cells, NK and iNKT cells have the capacity to kill cancer cells but with lower risk of triggering adverse effects. If successful, off-the-shelf approaches could transform CAR-T therapy from a highly individualized treatment into a scalable, ready-to-use product that is accessible for patients around the world.

For Emily Whitehead, CAR-T therapy meant the difference between exhausted treatment options and a cancer free life. When striving to create more success stories like this, it’s important to ask ourselves not only how we can push the scientific frontier to develop novel treatments, but how we can ensure these treatments are accessible to patients across the globe.