Unlocking the Power of CAR-T Cells: Revolutionizing Cancer Treatment

Car T-Cells

T-Cells are an essential part of the immune system that protect the body from infection and diseases like cancer. However, T-Cells often fail to recognize the Cancer Cell due to the similarity of the cancer cell with normal somatic cells. Therefore, CAR T-Cell therapy was created to allow the T-Cell to obtain the ability to identify Cancer cells and distinguish them from healthy cells. CAR T-Cell therapy involves genetically engineered T-Cells that target and destroy cancer cells. The process of CAR T-Cell therapy involves the collection of T-cells from the patient’s bloodstream, genetic modification of t-cells, and infusion of the CAR T-cells into the patient. T-cells will be withdrawn and removed from specific blood components such as white blood cells from the patient’s blood through the process called apheresis. Subsequently, the extracted T-cells will be engineered in the lab by introducing genes that allow T-cells to produce chimeric antigen receptors (CARs) on their surface. CARs are proteins that allow the T-cells to recognize and bind to specific proteins on the Cancer cells. Next, the genetically modified T-cells will be cultured and grow into millions of CAR T-cells that will be infused back to the patient, expecting the CAR T-cells to effectively identify and attack the specific cancer cells.  

CAR T-Cell Therapy Research Development  

Currently, the U.S. Food and Drug Administration has approved six CAR T-Cell therapies to treat blood cancers that include some forms of leukemia, lymphomas, and multiple myeloma. These CAR T-Cell therapies are Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), Yescarta (axicabtagene ciloleucel), and Carvykti (ciltacabtagene autoleucel). CAR T-Cells possess continuous potential in research and medical treatment. CAR T-Cells offer a high efficacy in hematological malignancies that demonstrates remarkable success in treating blood cancers and achieving high remission rates in patients with relapsed and refractory disease. In addition to cancer treatment, there has been research conducted that explores the potential of CAR T-Cells in tumor development with promising results in the early clinical trials. Present research also combined CAR T-Cell therapy with other medical treatments such as Checkpoint inhibitors to develop enhancement of antitumor activity. Beyond cancer treatment, CAR T-Cells have displayed significant roles in autoimmune disease and infection disease to target specific immune cells and viruses, respectively. In summary, CAR T-Cells illustrate a great potential in both research and medical development.  

Moffit Cancer Center, image of patient receiving Car T-Cell therapy

Side Effecta of CAR T-Cell Therapy 

Although CAR T-Cell Therapies have displayed a significant and promising potential, it is imperative to recognize the possible health implications of such innovation. Most of the side effects for this treatment depend on the type of CAR T-Cell therapy that the patient had received. For instance, patients may develop Cytokine Release Syndrome (CRS) as the CAR T-Cell stimulates the immune system to produce large amounts of cytokine. Sometimes, patients can also suffer from neurotoxicity or allergy due to CAR T-Cell therapies. Additionally, CAR T-Cell therapies may result in an increased risk of infection. CAR T-Cells that are designed to recognize the CD19 protein on the Cancer cells may target B cells–a type of white blood cell fighting against infection–that contain large amounts of CD19 proteins on their surface. As a result, healthy B cells can be destroyed alongside the cancerous cells, causing patients to be more easily exposed to pathogens. Another side effect is tumor lysis syndrome that results from the breakdown of cancer cells by the CAR T-Cells. Chemicals including potassium, sodium, phosphate, and uric acid are essential for blood streams health maintenance. Tumor Lysis Syndrome can cause abnormal levels of these chemical components which can upset a patient’s heart rhythm and kidney function 3.  

However, with the constant developments in research, there are promising solutions to address these implications. For example, current research has been focusing on mitigating the toxicities in CRS and neurotoxicity, such as dose adjustment and supportive care. There are also treatments such as Immunoglobulin therapy to induce antibodies to fight infection, and medicine that help to reduce the levels of uric acid in the blood to combat Tumor Lysis Syndrome.  

CAR T-Cell Therapy's Effect on the Economy  

CAR T-Cell therapy offers a promising cancer immunotherapy treatment that can improve the overall economic development with the reduction of diseases such as cancer, autoimmune and infectious disease. However, the high costs and other challenges raise the concerns of the public regarding the accessibility and affordability of such innovation to the patients, payers, and healthcare system. One-time administrations of CAR T-Cell therapy in the United States costs between $424,000 and $543,828. However, the total cost of care can be much higher, sometimes reaching $1 million or more with hospital stays and supportive care (4). Accompanied with limited insurance converage in many populations, CAR T-Cell therapy is not affordable for every individual currently.   

However, recent studies suggested that CAR T-Cell therapy has demonstrated a gained social value of $6.5 billion and $34.8 billion for pediatrics with a net social value gain of $952,991 per child treated, even after including costs for production and treatment. While treatment delays may decrease, these delays may negatively affect the social value generated by CAR T-cell therapy, with a 1-, 2-, or 6-month treatment delay leading to a 9.8%, 36.2%, or 67.3% loss of social value for pediatrics patients and a 4.2%, 11.5%, or 46.0% loss of social value (1). Therefore, timely patient access to CAR T-Cell therapies is essential to reach the social value level.  

Social Concerns 

There exist various social concerns regarding CAR T-Cell therapies. These concerns do not merely include the socioeconomic disparities, which patients with lower socioeconomic status are unlikely to receive CAR T-cell treatment, but also include racial and ethnic disparities. Studies have suggested that Africans and Americans were less likely to receive CAR T-Cell therapies than other race/ethnicity groups (2). Therefore, in order to increase the social value and reach a greater potential of CAR T-Cell therapies in research, medical, and economic development, these social concerns need to be addressed. These concerns can be minimized by moving treatment from academic medical centers to community-based hospital or oncology clinics, manufacturing CAR T-cells locally to eliminate the cost for shipping and cryopreservation, reducing the health-care burden with outpatient administrations, or expanding patient assistance programs. Individuals can also participate in educating patients regarding potential expenses and financial assistance to increase health literacy in the community.  

References 

1 Abou-el-Enein, M. & Gauthier, J. (2022). The Value of CAR-T-cell Immunotherapy in Cancer. In: N. Kröger, J. Gribben, C. Chabannon et al. (Eds.), The EBMT/EHA CAR-T Cell Handbook [Internet] (pp. 231-234). Springer. https://doi.org/10.1007/978-3-030-94353-0_46  

2 Ahmed, N., Shahzad, M., Shippey, E., Bansal, R., Mushtaq, M. U., MahmoudJafari, Z., Faisal, M. S., Hoffmann, M., Abdallah, A., Divine, C., Hamadani, M., McGuirk, J., & Shune, L. (2022). Socioeconomic and racial disparity in chimeric antigen receptor T Cell Therapy access. Transplantation and Cellular Therapy, 28(7), 358-364. https://doi.org/10.1016/j.jtct.2022.04.008  

3 Cancer Research UK. (2024, September 25). CAR T-Cell Therapy. https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/CAR-T-cell-therapy 

4 Thavorn, K., Thompson, E. R., Kumar, S., Heiskanen, A., Agarwal, A., Atkins, H., Shorr, R., Hawrysh, T., Chan, K. K., Presseau, J., Ollendorf, D. A., Graham, I. D., Grimshaw, J. M., Lalu, M. M., Nochaiwong, S., Fergusson, D. A., Hutton, B., Coyle, D., & Kekre, N. (2024). Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review. Value in health: the journal of the International Society for Pharmacoeconomics and Outcomes Research, 27(8), 1149–1173. https://doi.org/10.1016/j.jval.2024.04.004