Immunotherapy for Acute Lymphoblastic Leukemia: Challenge and Promise

Acute Lymphoblastic Leukemia (ALL) comprises 80% and 20% of pediatric and adult leukemias, respectively. Treatment is successful in 80% children with ALL but the survival of relapsed cases is poor. In adults, the relapse rate is over 50% and the overall survival is 20-40%. Relapse, mainly due to multidrug resistance, is the major concern in acute leukemias. Chemotherapy intensification has largely improved the survival of children with ALL, but despite this modification, most of the relapsed cases will die. In addition, intensive regimes have high toxicity and several side effects and it might not feasible for the adult. Therefore, the development of novel therapeutic approaches is critical. One of these strategies is immunotherapy. In this paper, written in Iran, by reviewing 50 newest references (2005-2017) using Elsevier, OVID and Pubmed databases, different kind of immunotherapeutic approaches for ALL including antibody and cellular based therapies (such as naked antibodies, bi-specific T-cell engaging antibodies, antibody– drug conjugates, chimeric antigen receptor (CAR)-modified T cells, natural killer and DC-based and radioimmunotherapy) are briefly introduced. The promising trials are highlighted and the Abs based-immunotherapy-related challenges such as monoclonal Abs toxicities, immunogenicity, and the mechanisms of immunotherapy resistance are discussed. Finally, cellular based-immunotherapy-related problems such as cytokine release syndrome and other challenges are reviewed.