Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia
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Strategies for having a more effective and less toxic CAR T‑cell therapy for acute lymphoblastic leukemia Mohadese Hashem Boroojerdi1 · Fatemeh Rahbarizadeh1,2 · Pouya Safarzadeh Kozani3,4 · Elahe Kamali1,5 · Pooria Safarzadeh Kozani1 Received: 28 July 2020 / Accepted: 30 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In the recent years, using genetically modified T cells has been known as a rapid developing therapeutic approach due to the heartwarming results of clinical trials with patients suffering from relapsed or refractory (R/R) hematologic malignancies such as R/R Acute Lymphoblastic Leukemia (R/R ALL). One of these renowned approaches is Chimeric antigen receptors (CARs). CARs are synthetic receptors with the ability to be expressed on the surface of T lymphocytes and are specifically designed to target a tumor-associated antigen (TAA) of interest. CAR-expressing T cells have the capability of proliferating and maintaining their immunological functionality in the recipient body but like any other therapeutic approach, the safety, effectiveness, and specificity enhancement of CAR T cells still lingers in the ambiguity arena. Genetic manipulation methods, expansion protocols, infusion dosage, and conditioning regimens are all among crucial factors which can affect the efficacy of CAR T cell-based cancer therapy. In this article, we discuss the studies that have focused on various aspects that affect the efficacy and persistence of CAR T-cell therapy for ALL treatment and provide a widespread overview regarding the practical approaches capable of elevating the effectiveness and lessening the relative toxicities attributed to it. Keywords Chimeric antigen receptor · CD19 · Acute lymphoblastic leukemia · Immunotherapy
Introduction Acute lymphoblastic leukemia (ALL) has been known as the most common cancer in children and the most frequent cause of cancer-related death in patients with less than
* Fatemeh Rahbarizadeh [email protected] 1
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115‑331, Tehran, Iran
2
Research and Development Center of Biotechnology, Tarbiat Modares University, Tehran, Iran
3
Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
4
Student Research Committee, Medical Biotechnology Research Center, School of Nursing, Midwifery, and Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
5
Division of Genetic, Biology Department, Faculty of Sciences, Isfahan University, Isfahan, Iran
20 years of age [1]. In the United States, approximately 6000 cases of ALL are diagnosed annually, half of which comprised children and teenager cases [2]. Thrombocytopeniarelated bruising or bleeding, infections caused by neutropenia, and anemia-related pallor and fatigue are all among common symptoms of ALL [2]. Spleen, liver, lymph node, and mediastinum leukemic infiltration have also been k
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