Dr. William B. Colley, hailed as the “Father of Cancer Immunotherapy,” started injecting live bacteria into cancer patients in the 1890s (Mitra et al., 2023). In 1993, Israeli immunologist Zelig Eshhar created T cells with the first chimeric model, later known as the first generation of CARs (Memorial Sloan Kettering Cancer Center [MSKCC], n.d.). Finally, in 2002, the MSK team engineered the effective CAR-T cells, successfully surviving, proliferating, and killing cancer cells in-vitro, opening up the field of CAR-T cell therapy (MSKCC, n.d.). However, what are CAR-T cells or CAR-T cell therapy, and why are they so different from normal cancer therapies? 

Chimeric Antigen Receptor (CAR-T) cell therapy is a transformative breakthrough in cancer research and immunotherapy, as, instead of the usual treatments that kill cancer cells along with some healthy cells, CAR-T involves genetically engineering patients’ own T cells, which are the body’s primary killer of infected cells, to target cancer cells (Alsaieedi and Zaher, 2025). The process involves taking the T cells in-vitro and adding a special gene for a receptor called chimeric antigen receptors (CAR), then finally infusing them back into the patient (Merit Cro, n.d.). The CARs help the T cells bind to specific proteins in cancer cells called antigens, guiding them to kill any cancer cells with the target antigens (National Cancer Institute [NIH], 2025). This entire process takes around three to five weeks (NIH, 2025). 

​

Many generations of CAR-T cells have been created since the 1980s, and the first CAR-T cell therapy was approved by the FDA on August 30, 2017, for the treatment of a Leukemia patient (Mitra et al., 2023). In February 2022, Carl June and David Porter of the University of Pennsylvania (UPenn) reported two patients in remission for twelve years after being treated

with CAR-T cell therapy, demonstrating that CAR-T cell therapy could actually cure some leukemia patients (Merit Cro, n.d.). 

However, like all other cancer treatments, CAR-T cell therapies have limitations and side effects. One immediate side-effect includes cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (Mitra et al., 2023). In CRS, the engineered T cells fill the bloodstream with cytokines, which help stimulate and guide the immune response (NIH, 2025). Its overabundance, however, can cause high fevers and drops in blood pressure and can sometimes even be fatal (NIH, 2025). A CAR-T gene cell therapy trial was discontinued recently due to two patient deaths (Merit Cro, n.d.). ICANS can produce confusion, sleepiness, and impaired speech, but both of these syndromes can be treated with steroids (NIH, 2025). 

Moreover, current CAR-T cell therapy is extremely expensive, due to the high cost of manufacturing the CAR-T cells, resulting in treatment costs of up to $500,000 (Mitra et al., 2023). There is also a limited number of institutions that can provide CAR-T treatment, as the therapy involves a lot of complex steps (Merit Cro, n.d.). The process also takes quite a long time, from two to eight weeks, during which patients could succumb to their disease (Mitra et al., 2023). 

​

Most importantly, although solid tumors are present in 90% of adult cancer patients and 30% in children, CAR-T has been far less effective against tumors compared to its unprecedented success against hematological cancers (Mitra et al., 2023). So far, the FDA has approved six CAR-T cell therapies, yet CAR-T cell therapies for solid tumors have remained in the experimental phase (Merit Cro, n.d.). A major issue is that researchers are currently unable to identify antigens on solid tumors that are not on healthy cells for the CARs to target (NIH, 2025). Additionally, the immunosuppressive tumor environment (TME) in tumors can produce molecules that cause the CAR-T cells to malfunction or stop them from even reaching the tumor (NIH, 2025). The biggest obstacle, though, is tumor heterogeneity, which is that tumors of the same cancer can molecularly differ between patients, and even within the same one (NIH, 2025). An example of this problem is that some tumor cells do not have targetable antigens, or that they do not have enough of them for CAR-T cells to work (NIH, 2025). 

​

A more specific example is acute myeloid leukemia (AML), the most common acute leukemia present in adults and the elderly (Zugasti et al, 2025). There is no ideal target antigen on AML, as AML cells share most of their surface antigens with healthy hematopoietic stem and progenitor cells (HSPCs), and targeting them both at once can be life-threatening (Zugasti et al, 2025). 

Many also worry about the long-term safety of CAR-T cell therapy, such as T cell malignancies and cellular transformation (Patel et al., 2025). At UPenn, researchers determined that infusions of autologous, individualized, engineered T cells have a low risk of transformation, but infusions of allogeneic, off-the-shelf, T cells have been reported to cause graft-vs-host disease (GvHD), especially when created at high insertion copy numbers with a transposon system (Patel et al., 2025). To lower this risk, TCR genes are removed from the CAR-T cells using CRISPR, but the resulting allo-CAR-T cells do not last long in vivo, greatly reducing their efficacy (Mitra et al., 2023). 

​

Scientists have been working hard to mitigate these limitations, trying to improve the production and delivery methods of CAR-T cells and find ways to target solid tumors. A possible development of production brought up was transitioning from using the specific patient’s T cells and instead using the T cells of a healthy donor, allowing researchers to manufacture CAR-T

cells for potentially dozens at once, lowering costs and spreading the treatment further as the cells can be preserved on ice (Merit Cro, n.d.). Researchers at Penn Medicine are attempting to shorten manufacturing time by introducing a pre-clinical study of functional CAR-T cells that were grown within 24 hours (Merit Cro, n.d.). Several scientists are also researching in-vivo approaches, such as those at the Multifunctional Alginate Scaffold for T Cell Engineering and Release (MASTER) at UNC-Chapel Hill University and North Carolina State University, which creates and releases CAR-T cells within the body (Merit Cro, n.d.). Generation of CAR-T cells in vivo removes the need for ex-vivo engineering, reducing production costs and time (Mitra et al., 2023). 

​

Regarding targeting solid tumors, researchers have also made many advancements and reported promising results. A group at Stanford has already reported encouraging findings in a trial of CAR-T cell therapy in some patients with diffuse midline glioma, a fatal brain cancer (NIH, 2025). Other trials testing CAR-T cell therapies in solid cancers like ovarian and colorectal also show positive results (NIH, 2025). Companies such as BioNTech and Mayo Clinic are developing innovative tactics as well, such as “armored” CARs to penetrate the TME (Merit Cro, n.d.). 

​

The achievement of CAR-T cell therapy has already inspired scientists to delve deeper into the field of engineering immune cells (Mitra et al., 2023). Refining CAR-T cell therapies is also developing at a quick pace, as more and more treatments are created to lessen side effects and increase efficacy (NIH, 2025). With CAR-T, scientists even imply that patients could be spared two entire years of chemotherapy (NIH, 2025). Overall, research in CAR-T is ongoing, but we can look forward to continued progress, helping treat cancer and other diseases to improve the health of patients around the globe.

​

​

​

​

​

References 

Alsaieedi, A. A., & Zaher, K. A. (2025, July 16). Tracing the development of CAR-T cell design: from concept to next-generation platforms. Frontiers. Retrieved January 18, 2026, from https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1615212/f ull 

Memorial Sloan Kettering Cancer Center [MSKCC]. (n.d.). CAR T Cells: Timeline of Progress. Memorial Sloan Kettering Cancer Center. Retrieved January 18, 2026, from https://www.mskcc.org/timeline/car-t-timeline-progress 

Merit Cro. (n.d.). A Rundown of New Developments in CAR T-cell Therapy. Merit. Retrieved January 18, 2026, from 

https://meritcro.com/a-rundown-of-new-developments-in-car-t-cell-therapy/

Mitra, A., Barua, A., Huang, L., Ganguly, S., Feng, Q., & He, B. (2023, May 15). From bench to bedside: the history and progress of CAR T cell therapy. PubMed Central. Retrieved January 18, 2026, from https://pmc.ncbi.nlm.nih.gov/articles/PMC10225594/

National Cancer Institute [NIH]. (2025, February 26). CAR T Cells: Engineering Immune Cells to Treat Cancer. National Cancer Institute. Retrieved January 18, 2026, from https://www.cancer.gov/about-cancer/treatment/research/car-t-cells 

Patel, K. K., Tariveranmoshabad, M., Kandu, S., Shobaki, N., & June, C. (2025, May 7). From concept to cure: The evolution of CAR-T cell therapy. Molecular Therapy. Retrieved January 18, 2026, from 

https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016% 2825%2900179-0

Zugasti, I., Espinosa-Aroca, L., Fidyt, K., Mulens-Arias, V., Diaz-Beya, M., Juan, M., Urbano-Ispizua, Á., Esteve, J., Velasco-Hernandez, T., & Menéndez, P. (2025, July 4). CAR-T cell therapy for cancer: current challenges and future directions. Signal Transduction and Targeted Therapy. Retrieved January 18, 2026, from https://www.nature.com/articles/s41392-025-02269-w