Harnessing autologous immune effector mechanisms in acute myeloid leukemia: 2023 update of trials and tribulations.

Numerous recent advances have been made in therapeutic approaches toward acute myeloid leukemia (AML). Since 2017, we have seen eleven novel Food & Drug Administration (FDA)-approved medications for AML, all of which extend beyond the classical cytarabine-based cytostatic chemotherapy. In the recent two decades, the role of immune surveillance in AML has been intensively investigated. The power of one's own innate and adaptive immunity has been harnessed pharmacologically toward the goal of clearance of AML cells. Specifically, pre-clinical studies have shown great promise for antibodies that disinhibit T cells and macrophages by blocking checkpoint receptors within the immunologic synapse, thereby resulting in the elimination of AML cells. Anti-CD33 CAR-T therapies and anti-CD3/CD123 bispecific antibodies have also exhibited encouraging results in pre-clinical and early clinical studies. However, despite these translational efforts, we currently have no immune-based therapies for AML on the market, with the exception of gemtuzumab ozogamicin. In this focused review, we discuss molecular target validation and the most relevant clinical updates for immune-based experimental therapeutics including anti-CD47 monoclonal antibodies, CAR-T therapies, and bispecific T cell engagers. We highlight barriers to the clinical translation of these therapies in AML, and we propose solutions to optimize the manufacturing and delivery of the most novel immune-based therapies in the pipeline.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest SAP served on the Acute Myeloid Leukemia Advisory Board and the COMMANDS Advisory Board for Bristol Myers Squibb. SAP served on the Multiple Myeloma Advisory Board for Pfizer. JMG serves on the Advisory Board for Novartis and holds U.S. Patent No. 9012,215, U.S. Patent No. 10,222,376, and U.S. Patent No. 11,209,435. JC serves on advisory boards for Jazz Pharmaceuticals, Pfizer, MERIT CRO, and Amgen; serves as a Data Safety Monitoring Board Member with ICON-AlloVir and ICON-Prolacta; owns stock in Actinium Pharmaceuticals, Bluebird Bio/2Seventy, Dynavax Technologies, aTyr Pharma, Gamida Cell, Miragen Therapeutics, Mustang Bio, Novavax, Ovid Therapeutics, Sorrento Therapeutics, TG Therapeutics, Vaxart, and Veru. All other authors declare no conflicts.