Cell Biology

CAR-T Cell
 
Jonee Grant
Cell Bio BIOL 293
February 27, 2026
 

Medicine keeps advancing significantly and new breakthroughs continue to emerge. One of those breakthroughs comes in the form of cell therapies used to combat cancer and disease in a unique way. A unique cell being used is the CAR-T cell. A CAR is an enhancement added to a T-cell used in immunotherapy. The patients’ own T-cells are modified by adding the Chimeric Antigen Receptor CAR. The addition of the CAR gives the T-cells the proper surface structure to bind to certain cancer cells and kill them (1). CAR-T cells are used in treatments for Tripple negative Breast Cancer and non-Hodgkin lymphomas as well as other hematological malignancies. As with any medical intervention there are some side effects of CAR cell treatments. Also, cell therapy is not always applicable as it depends on the patient’s T-cell count to be adequate and a healthy immune system.

CAR-T therapy is a multi-step process, with the therapy spanning over 1-2 months with once daily infusions. The patient’s blood is drawn, and the white blood cells are put into a centrifuge to separate the T-cells from the blood. The CAR is added to the T-cell. The modified T-cell is then reintroduced into the patients’ blood stream intravenously (1). The T-cells can now bind to the cancer cell. CAR T cells can be derived either autologously from T cells in a patient’s own blood or allogeneically from a donor. Once isolated, these T cells are genetically engineered to express a specific CAR, using a vector derived from an engineered lentivirus such as HIV. The CAR programs the T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor cell but not on healthy cells.

Tripple Negative Breast Cancer or TNBC is an aggressive type of breast cancer where the. Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification that comprises 15–20% of all breast cancer cases.  Limited treatment options for TNBC make cell therapies important. Immune checkpoint pathways regulate T-cell responses at distinct stages of the antitumor immune response, CTLA-4 primarily functions during the early “priming” phase in secondary lymphoid organs, where it competes with CD28 for binding to B7 molecules (B7-1/CD80 and B7-2/CD86) on antigen-presenting cells, thereby limiting initial T-cell activation (2). These bonding sites are part of the immune checkpoint. The major histocompatibility complex (MHC) a genetic region that helps the immune system tell itself apart. By allowing peptides to be displayed on the cell surface the T-cell receptors can determine if a cell is abnormal. The tumor and the immune T-cell express the protein PD-L1 and PD-1, respectively. The T-cells PD-1 is an inhibitor that limits tissue damage and prevents autoimmunity. Some tumor cells have evolved to bond their PD-L1 to different sites on the T-cell causing T-cell exhaustion. The result is that the tumor cell is now able to get past the immune checkpoint. T-cell exhaustion causes a reduced ability to kill the tumor cell. Low cytokine production results in weak immune signaling and suppressed cytotoxic activity results in the tumor escaping the immune system (2). Some Patients with TNBC are at a higher risk of having the mutation BRCA1, this mutation maybe hereditary. Approximately 10–20% of TNBC patients harbor germline or somatic breast cancer susceptibility gene 1 and 2 (BRCA1/2) mutations or exhibit homologous recombination deficiency (HRD), which contributes to genomic instability, TMB, and increased neoantigen load (3).

CAR-T cell therapy is considered by some as a living drug as it expands and multiplies through the body. It actively seeks out cells to be destroyed, and it can remain in the body long term (3). Low activity of MHC is what causes cancer cells to bypass the immune system. CAR-T cells can bind to cancer cells without the MHC. By using a single chain variable fragment as a sensor, it binds to the tumor and kills it. The CAR programs the T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor cell but not on healthy cells. The surface of CAR T cells can bear either of two types of co-receptors, CD4 and CD8, which have different and interacting cytotoxic effects. When CAR T cells come in contact with their targeted antigen on a cell’s surface, T cells bind to it and become activated, then proceed to proliferate and become cytotoxic, destroying the cancer cells through several mechanisms However, drawbacks include limited targeting of intracellular antigens and the risk of treatment failure (3). While CAR-T cell therapy is groundbreaking, there are limitations. CAR cells are not effective on intercellular antigens as they are not present on the cells’ surface and CARs only bind to surface proteins. The quality of the patients’ T cells plays a major factor in the effectiveness. There is also cost and patient accessibility to consider. To combat some of these hurdles, batch manufacturing is considered. This would require donation of blood containing healthy T-cells. Which could lead to lower cost and better accessibility. While autologous CAR-T cells remain the primary clinical application, advances in genome engineering and production methods are paving the way for more efficient and cost-effective allogeneic CAR-T cell therapies (3).
There are five generations of CAR cells since its development in 1987.Some studies show that CAR-T cell therapy aimed at CD19 has reconfigured treatment for B-cell malignancies. B-Cell malignancies are cancers that arise from B lymphocytes which are responsible for producing antibodies. This can cause cancers such as non-Hodgkin lymphomas. In a study of CAR-T cell effectiveness against CD19, magnetic activated cell sorting was used to isolate CAR-T products to determine how each subtype aides in killing the tumor. The results showed that CAR‑T cells can dampen therapeutic responses and may contribute to resistance.

To conclude, CAR‑T cell therapy demonstrates noteworthy progress in modern cancer treatment, offering a targeted approach to how the immune system can be harnessed against disease. Adverse reactions to the treatment are possible, these reactions can affect any organ system, with common involvement of the skin, gastrointestinal tract, endocrine glands, lungs, and liver (2). There are serious side effects that result from CAR T-cells being introduced into the body, including cytokine release syndrome and neurotoxicity. Because it is a relatively new treatment, there are few data about the long-term effects of CAR T-cell therapy, meaning there are still concerns about long-term patient survival Even though cell therapy is not without limitations, ongoing research, improved manufacturing methods, and next‑generation CAR designs continue to address these challenges. There are over 400 ongoing clinical trials happening globally involving CAR T cells, with most of those trials target blood cancers. CAR T therapies account for more than half of all trials for hematological malignancies. CD19 continues to be the most popular antigen target, followed by BCMA.