AML—is it time to drive a CAR(-T)?

Abstract

The treatment options for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) have substantially improved over the last 5 years. However, even though novel targeted agents (e.g. venetoclax, IDH1/2 and novel FLT-3 inhibitors; cytosolic isocitrate dehydrogenase 1/2 and fms-like tyrosine kinase 3 inhibitor) and improved chemotherapeutics (e.g. CPX-351; liposomale Daunorubicin/ Cytarabine) are entering clinics, physicians are still confronted with high relapse and treatment failure rates. Thus, novel new strategies are required to improve AML therapy. Application of genetically engineered T cells (i.e. chimeric antigen receptor T cells, CART cells) has proven to be highly effective in B cellderived neoplasia and early data suggest also a high potential in the treatment of AML. This short review highlights the current approaches but also limitations of CART cell therapy in AML precluding their current routine clinical use. Among a plethora of problems to be overcome, a critical issue will be to find relatively selective actionable targets in AML. Keywords Relapsed/refractory AML • CD123 • CD33 • CD135 • TCR-C4 CAR transgenic T cells have led to impressive clinical results in treating patients with relapsed and refractory B cell leukemia and lymphoma [1-3]. To date,

Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8+ T cell cytokine production

“…One approach to enforce tumor recognition by T cells is by making use of chimeric antigen receptors, or CARs 134,138,139 . A CAR is constructed from the variable region of a high affinity tumor antigen‐specific antibody targeting a tumor antigen, that is CD19 or CD33, 136,140 coupled to the signalling domain of CD3 and the signalling domain of one or more costimulatory molecules, for example CD28. As a result, T cells can be equipped with a CAR which serves as a complete signalling module for T cell activation 138 …”

Combination of an Oxindole Derivative with (−)-β-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells

“…It is reported that FLT3 inhibitors have demonstrated promising results in clinical settings with minimal side effects [ 17 , 18 ]. The standard treatment option includes chemotherapy and a bone marrow (BM) transplant [ 19 ].…”

CAR(-T)s are on the road

“…Finally, Rudzki et al focused on the importance of CAR-T cell therapy in r/r AML (acute myeloid leukemia), illustrating current results and providing an overview of the most promising cellular strategies to handle r/r AML with CAR-T cell-or TCRapproaches [4].…”