Traditional cancer treatments like surgery, chemotherapy, and radiation therapy have been fundamental for many years. However, recent advances have introduced new approaches to cancer care. The 2000s brought targeted therapies, like imatinib and trastuzumab, which focus on specific molecular changes in cancer cells, becoming standard treatments for various cancers. In the last decade, immunotherapy has gained prominence, bolstering the immune system's ability to shrink or eliminate tumors, and providing long-lasting responses for some patients. Immune checkpoint inhibitors are already widely used for many cancer types, while chimeric antigen receptor (CAR) T-cell therapy (cancer.gov, 2022), (Levine et al., 2017; Shah and Fry, 2019; Sterner and Sterner, 2021; Maakaron et al., 2022), though less common, shows promise in eradicating advanced leukemias and lymphomas, offering extended cancer control.

Since 2017, a few CAR T-cell therapies have been approved in both the United States by the U.S. Food and Drug Administration (FDA) (cancer.gov, 2022) and the European Union by the European Medicines Agency (EMA). All these therapies have received approval for treating blood-related malignancies, which encompass lymphomas, certain types of leukemia, and, most recently, multiple myeloma. While these treatments have generated considerable enthusiasm, they result in sustained survival for less than 50% of treated patients. Additionally, they have faced scrutiny due to their high cost. Nonetheless, after extensive and meticulous research, CAR T-cell therapies have transitioned into the mainstream of cancer care. They are now readily accessible in various countries in addition to the United States, and the European Union, establishing themselves as a standard treatment for individuals dealing with aggressive lymphomas.

CAR T-cell therapies represent a revolutionary type of living drug therapy that harnesses the potent capabilities of T-cells, which play a central role in orchestrating the immune response and directly eliminating infected cells (cancer.gov, 2022), (Maakaron et al., 2022). The fundamental concept of CAR T-cell therapy is depicted in Fig. 1. Currently, CAR T-cell therapies are custom-tailored for each patient. This process involves harvesting the patient's T-cells and reengineering them in a laboratory to express specialized synthetic proteins on their surface, known as chimeric antigen receptors. These CARs are meticulously designed to exclusively identify and bind to specific proteins or antigens located on the surface of cancer cells. It is crucial to emphasize that these receptors are entirely artificial and not naturally occurring. After the modified T-cells are cultured in the lab, they are multiplied into millions and subsequently reintroduced into the patient. In an ideal scenario, the CAR T-cells will proliferate within the patient's body, guided by their engineered receptors to seek out and eliminate cancer cells bearing the targeted antigen on their surfaces. Currently, FDA-approved CAR T-cell therapies primarily focus on targeting one of two antigens present in B cells, namely CD19 (CD19, or Cluster of Differentiation 19, a cell surface protein expressed on B cells) (Ying et al., 2019; Park et al., 2016), or BCMA (B-cell maturation antigen, a cell surface protein predominantly found on mature B cells) (Raje et al., 2019; Roex et al., 2020).

The process of crafting CAR T-cell therapies encompasses several stages, and as an increasing number of CAR T-cell therapies are being developed and assessed in clinical trials, they share common components (cancer.gov, 2022), (Maakaron et al., 2022). These CARs extend through the cell membrane, with one part of the receptor positioned outside the cell and the other within it. The outer segment of the CAR typically comprises segments or domains derived from synthetic antibodies engineered in the laboratory. These specific domains are carefully chosen for their pivotal role in how efficiently the receptor can recognize and bind to the antigens found in tumor cells. Within the CAR, there are signaling and co-stimulatory domains that transmit signals into the cell when the receptor engages with an antigen. The selection of these various domains can significantly impact the overall functionality of the cells.