There are serious side effects that result from CAR T-cells being introduced into the body, including cytokine release syndrome and neurological toxicity. Because it is a relatively new treatment, there is little data about the long-term effects of CAR T-cell therapy. There are still concerns about long-term patient survival, as well as pregnancy complications in female patients treated with CAR T-cells. Anaphylaxis may be a side effect, as the CAR is made with a foreign monoclonal antibody, and as a result provokes an immune response. On-target/off-tumor recognition occurs when the CAR T-cell recognizes the correct<unk> , but the<unk>  is expressed on healthy, non-pathogenic tissue. This results in the CAR T-cells attacking non-tumor tissue, such as healthy B cells that express CD19. The severity of this adverse effect can vary from B-cell aplasia, which can be treated with supporting infusions, to extreme toxicity leading to death. There is also the unlikely possibility that the engineered CAR T-cells will themselves become transformed into cancerous cells through insertional mutagenesis, due to the viral vector inserting the CAR gene into a tumor suppressor or oncogene in the host T cell's genome. Some retroviral (RV) vectors carry a lower risk than lentiviral (LV) vectors. However, both have the potential to be oncogenic. Genomic sequencing analysis of CAR insertion sites in T cells has been established for better understanding of CAR T-cell function and persistence in vivo. Cytokine release syndrome The most common issue after treatment with CAR T-cells is cytokine release syndrome (CRS), a condition in which the immune system is activated and releases an increased number of inflammatory cytokines. The clinical manifestation of this syndrome resembles sepsis with high fever, fatigue, myalgia, nausea, capillary leakages, tachycardia and other cardiac dysfunction, liver failure, and kidney impairment. CRS occurs in almost all patients treated with CAR T-cell therapy; in fact, the presence of CRS is a diagnostic marker that indicates the CAR T-cells are working as intended to kill the cancer cells. The severity of CRS does not correlate with an increased response to the treatment, but rather higher disease burden. Severe cytokine release syndrome can be managed with immunosuppressants such as corticosteroids, and with Tocilizumab, an anti-IL-6 monoclonal antibody. Immune effector cell-associated neurotoxicity Neurological toxicity is also often associated with CAR T-cell treatment. The underlying mechanism is poorly understood, and may or may not be related to CRS. Clinical manifestations include delirium, the partial loss of the ability to speak coherently while still having the ability to interpret language (expressive aphasia), lowered alertness (obtundation), and seizures. During some clinical trials, deaths caused by neurotoxicity have occurred. The main cause of death from neurotoxicity is cerebral edema. In a study carried out by Juno Therapeutics, Inc., five patients enrolled in the trial died as a result of cerebral edema. Two of the patients were treated with cyclophosphamide alone and the remaining three were treated with a combination of cyclophosphamide and fludarabine. In another clinical trial sponsored by the Fred Hutchinson Cancer Research Center, there was one reported case of irreversible and fatal neurological toxicity 122 days after the administration of CAR T-cells.
Chimeric antigen receptor T cell
Donor-specific antibody
Regulatory B cell
Memory B cell
Regulatory T cell
Naive T cell
Nonspecific immune cell
Cytokine-induced killer cell