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Clinical Implications of Anti-CD19 Chimeric Antigen Receptors (CAR) T Cell Therapy in Acute Lymphoblastic Leukemia (ALL)

Ali R Jazirehi1*, Tam N M Dinh, Zena Taraporewalla, Jahzeel L Paguntalan and Gary J Schiller

Acute Lymphoblastic Leukemia (ALL) is a cancer of white blood cells that is most prevalent among young children. Several environmental and genetic factors contribute to the occurrence of ALL, including radiation exposure, ethnicity, gender, and other genetic traits. Traditional treatment options include chemotherapy, radiation, and bone marrow transplant. More recently, a form of antibody-mediated immunotherapy using genetically engineered chimeric antigen receptor (CAR) T-cells has been used in several clinical trials with encouraging results. CAR T-cells allow for highly targeted treatment by inducing activation of the modified T-cells and stimulating an apoptotic response in target B-cells upon ligation with a given antigen target. Typically, modified CAR T-cells are capable of specific recognition of the B-cell surface marker CD19, a universally expressed oncogenic antigen found in many forms of B-cell acute lymphoblastic lymphoma. Because CD19 is not expressed in hematopoietic cells, successful CD19-targeted treatment would eradicate cancerous cells without damaging the hematopoietic system. Hematopoietic cells can therefore regenerate normal CD19+ B-cells following treatment, as these are also depleted by anti-CD19 CAR T-cells. With limited toxicities and significant efficacy, CD19-targeted CAR T-cell immunotherapy is a promising treatment approach for ALL.