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to identify “self”. CAR-T-cells also allow for antigens other than proteins, like carbohydrates and lipids to be recognized.

Limitations to CAR-T-cell therapy include the identification of tumor specific target antigens. The binding of CARs is limited to molecules present on the surface of tumor cells. To select optimal antigens for targeting, the antigen needs to be selectively expressed on tumor cells at high levels but not be expressed on the surface of important normal tissue. Another limitation is the suboptimal performance of CAR-T cells in the treatment of solid tumors as it is difficult to find tumor specific antigens that are highly and uniformly expressed. Also, CAR-T-cells have the possibility of becoming dysfunctional due to a hostile tumor microenvironment characterized by oxidative stress, nutritional depletion, acidic pH or hypoxia. The presence of inhibitory soluble factors and cytokines and suppressive immune cells can contribute to T-cell inhibition.

Using CAR-T cells for the treatment of cancer can induce various side effects including high fever, low blood pressure, infection, low blood cell count or a weak immune system. A commonly observed toxicity includes cytokine release syndrome, which is characterized by high fever, hypotension, hypoxia, and multi-organ toxicity. CAR‐T cell related encephalopathy syndrome is another toxicity that results in a toxic encephalopathic state with symptoms of confusion, delirium, and occasionally seizures.

CAR-T cell therapy has had success in treating hematologic cancers like B‐cell malignancies, including acute and chronic B‐cell leukaemias, and B‐cell non‐Hodgkin lymphomas. Using anti-CD19 CAR-T-cells, there was a reported 90% complete remission rate in patients with B cell acute lymphoblastic leukemia. CD19 is antigen recognized as a target for immunotherapy in B cell malignancies because of its l