CAR-T Therapy: Revolutionizing Cancer Treatment with Immune Engineering

In the continuous fight against cancer, treatment options have typically centered around surgery, chemotherapy, and radiation therapy. Although these traditional forms have found much success and continue to thrive, chimeric antigen receptor T-cell therapy, or CAR-T therapy, has marked a significant breakthrough in cancer treatment in recent years. Unlike these traditional treatments, CAR-T therapy provides a personalized approach to target and destroy cancer cells through the immune system. This article explores how CAR-T therapy works, its benefits and challenges, and what the future of CAR-T therapy might look like.

In the last decade, immunotherapy has become a standard cancer treatment. Immunotherapy utilizes the body’s immune system to recognize and attack cancer cells. Immunotherapy can boost the natural defense of the immune system through vaccines, it can inhibit immune checkpoints to allow immune cells to respond more strongly to cancer, and it can engineer immune cells like T-cells to attack cancer cells (Immunotherapy for Cancer - National Cancer Institute, 2015). This engineering of immune cells is how CAR-T therapy works. The first step in therapy is the removal of T-cells from the patient's blood. Once extracted, the cells are genetically modified, having a gene added for a synthetic receptor called the chimeric antigen receptor, or CAR (American Cancer Society, 2024). These receptors can recognize certain types of antigens on cancer cells’ surfaces. Sometimes, chemotherapy might be paired with CAR-T therapy. According to the American Cancer Society, chemotherapy before the infusion of the CAR-T cells allows for the lowering of the number of other immune cells, in turn giving the CAR-T cells more of a chance to activate to fight the cancerous cells (2024). Next, the CAR-T cells are multiplied by the millions in the lab, and “then infused back into the patient.” Finally, the cells will multiply further, hunting down and attacking cancer cells that have the target antigen on their surface with the help of the engineered receptors (National Cancer Institute, 2022).

The whole process of CAR-T therapy is quite short, which is one of the most significant advantages of CAR-T therapy compared to other methods of cancer treatment. After the infusion, two weeks of inpatient care at the max is needed. Furthermore, “most patients have a much more rapid recovery than after stem cell transplants in which aggressive chemotherapy is used” (Advantages of CAR-T Cell Therapy | Rutgers Cancer Institute of New Jersey, n.d.).

In addition to its time-effective process, CAR-T therapy has the potential for long-term remission. Because the modified CAR-T cells can remain in the immune system long-term, they “may recognize and attack cancer cells if and when there’s a relapse” (Advantages of CAR-T Cell Therapy | Rutgers Cancer Institute of New Jersey, n.d). Many patients with aggressive cancers have remained in remission after receiving CAR-T therapy, even after other methods had been unsuccessful.

Despite these striking benefits, CAR-T therapy faces three major challenges and risks. First, CAR-T therapy poses some major concerns about its side effects due to its potential for severe adverse events. Severe adverse events are medical complications that occur from cancer treatment that are potentially life-threatening. For instance, “two of the most common adverse events are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)” (Mitra et al., 2023). The first, CRS, occurs when the immune system’s response to infusion is too strong, releasing too many cytokines than necessary. This reaction can lead to life-threatening conditions like organ failure or neurological issues from inflammation in the brain.

On the other hand, ICANS occurs when the infused T-cells release inflammatory signals that disrupt the brain, leading to symptoms like confusion, seizures, and sometimes more serious developments like the swelling of the brain and comas. It is important to note that while both of these side effects are common in CAR-T therapy, they are not as likely to be life-threatening in most cases. Furthermore, both conditions are often treatable, particularly if detected early on. Apart from its side effects, CAR-T therapy also faces various financial challenges. The costs to manufacture CAR-T cells are quite expensive. According to the American Society of Clinical Oncology, production will exceed hundreds of thousands of dollars, “typically over $400,000 USD and sometimes over $1 million USD per patient” (Scheffer et al., 2023). The high costs can be attributed to the specific and complex nature of manufacturing autologous T-cells, which means cells that come directly from the patient. The steep price of CAR-T therapy also means that it has limited availability to areas and patients that can afford it. The final downside to CAR-T therapy is its ineffectiveness against solid tumors. Efforts to employ the use of CAR-T cells to treat the solid tumors that occur in the brain or breast have been mostly futile. These solid tumors cover about 90% of adult cancer patients and about 30% percent of child cancer patients, immediately limiting the implementation of this type of therapy to a relatively small group of cancer patients (Mitra et al., 2023). According to the National Cancer Institute, this fruitlessness can be attributed to the surrounding environments of solid tumors. Physical barriers prevent the infused T-cells from reaching these tumorous cells (2022). These solid tumors are also capable of producing molecules that can suppress the immune system, essentially stripping away the ability of the infused T-cells to attack and kill them.

In conclusion, CAR-T therapy is truly a monumental leap forward in cancer treatment due to its ability to precisely target disease via a patient's immune system. Despite not being an all-encompassing solution right now, it has still found much success in treating blood cancers. Developing research that addresses CAR-T therapy’s limitations surrounding its side effects, cost issues, and treatment versatility holds a monumental promise that CAR-T therapy might be the answer to more accessible, effective, and personalized cancer treatment.

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https://unsplash.com/photos/refill-of-liquid-on-tubes-pwcKF7L4-no