Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

Abstract

Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.

Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients

“…The application of CAR-T has been implicated in acute leukemia and non-Hodgkin's lymphoma, and it has made prominent progress in B-ALL during the past several years. Clinical studies in the United States and Europe illustrate that the CR rate to CAR-T therapy is around 90% in R/R B-ALL patients, which is similar to that in de novo B-ALL patients [8][9][10][11][12][13][14] . The survival profiles of R/R B-ALL patients have also been improved by CAR-T therapy, but with inevitable adverse events (such as cytokine release syndrome (CRS), B cell aplasia, neurotoxicity, and tumor lysis syndrome) 15,16 .…”

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

“…CAR T-cell therapy is increasingly becoming a key player in the treatment of malignant diseases. While clinical trials are still in high demand, the use of CAR T-cells in the therapy of hematologic oncology such as acute lymphoblastic leukemia or lymphoma is generally accepted worldwide [45]. By targeting CD19 antigen on B-cells using CAR T-cell therapy, clinicians attained durable remissions and clinical response in patients with B-cell non-Hodgkin lymphoma and acute lymphoblastic lymphoma [46].…”

CRISPR/Cas9 in Cancer Immunotherapy: Animal Models and Human Clinical Trials

“…The latter expressed less than 2% exhaustion and retention markers of the effector cells [ 65 ]. The use of animal models in the context of acute lymphoblastic leukemia also delivered better results for the treatment of B-Cell ALL with CARs [ 69 ].…”