Will CAR T cell therapy have a role in AML? Promises and pitfalls

Abstract

Relapsed and/or refractory acute myeloid leukemia (RR AML) has a dismal prognosis. While chimeric antigen receptor T cells (CART) have been successful in improving treatment outcomes for B-lineage acute lymphoblastic leukemia by targeting CD19, the success of this strategy necessitates a cell surface antigen whose depletion can be clinically tolerated. The primary barrier currently preventing the use of CART therapy for AML is the lack of a myeloid equivalent to CD19-that is, an "expendable" antigen. All currently known cell surface targets on leukemic blasts are shared with healthy hematopoietic stem and progenitor cells or their progeny. Hence, while targeting CD19-expressing cells leads to prolonged B-cell aplasia which is clinically benign, targeting myeloid antigens would lead to prolonged myeloablation which is not clinically tolerable. Creative solutions are being developed to try to circumvent these challenges, using not only CART but a range of adoptive cellular immunotherapy modalities and novel transplant-related approaches to try to extend the successes of CART therapy to patients with AML.

Keywords: AML; Adoptive cellular therapy; CAR T cells; Immunotherapy; Leukemia.