Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study

Abstract

Acute lymphoblastic leukemia (ALL) is a cancer-specific lymphoid cell. Induction and consolidation chemotherapy alone or in combination with different therapeutic approaches remain the main treatment. Although complete or partial remission of the disease can be achieved, the risk of relapse or refractory leukemia is still high. More effective and safe therapy options are yet unmet needs. In recent years’ new therapeutic approaches have been widely used. Hematopoietic Stem Cell Transplantation (HSCT) presents significant limitations and the outcome of the consolidation treatment is patient dependent. Side effects such as Graft versus Host Disease (GvHD) in allogeneic hematopoietic stem cell transplantation are extremely common, therefore, using alternative methods to address these challenges for treatment seems crucial. In the last decade, T cells genetically engineered with Chimeric Antigen Receptor (CAR) treatment for the ALL are largely studied and represent the new era of strategy. According to the Phase I/II clinical trials, this technology results seem very promising and can be used in the next future as an effective and safe treatment for ALL treatment. In this review different generations, challenges, and clinical studies related to chimeric antigen receptor (CAR) T-cells for ALL treatment are discussed.

Natural Killer Cell-Mediated Immunotherapy for Leukemia

“…While overall 5-year survival rates for leukemia remain high, treatment of relapsed leukemia remains a major obstacle as these patients often present with chemoresistance and a significantly impaired immune system [17,18]. CAR-T cell therapies have been explored for use in leukemia and have shown some success in recognition of cancer cells, but this form of treatment is often coupled with severe side effects including encephalopathy, coagulopathy, hypoxia, and neurotoxicity [19][20][21][22]. With the success of targeting the immune system for improved patient recovery, less toxic alternatives to CAR-T therapies are being actively explored.…”

Road testing new CAR design strategies in multiple myeloma

“…CAR T-cell success is exemplified by FDA-approval of the anti-CD19 CAR T-cell tisagenelcleucel for treatment of acute lymphoblastic leukemia (ALL) and axicabtagene ciloleucel for diffuse large B-cell lymphoma (DLBCL). In early 2021, liso-cel received FDA-approval for DLBCL, based upon significant efficacy and low toxicity ( 45 , 46 ).…”

“…CAR T-cell success is exemplified by FDA-approval of the anti-CD19 CAR T-cell tisagenelcleucel for treatment of acute lymphoblastic leukemia (ALL) and axicabtagene ciloleucel for diffuse large B-cell lymphoma (DLBCL). In early 2021, liso-cel received FDA-approval for DLBCL, based upon significant efficacy and low toxicity (45,46). CAR can be directed to the TRAC locus, resulting in uniform CAR expression, reduced tonic signaling, decreased exhaustion and increased antitumor efficacy and gives the added benefit of producing a potential universal product.…”

Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

“…Clinical trials conducted on patients with acute lymphocytic leukemia have shown a complete recovery in up to 92% of patients with very meaningful results ( 20 ). CAR-T cell therapy is being actively implemented for treating large B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia ( 22 , 23 ). Although this CAR-T cell therapy has achieved clinical success in some hematologic cancer patients ( 24 ), it has two main problems that need improvement.…”