| Autor: |
Acharya UH; Divisions of Hematologic Malignancies & Immune Effector Cell Therapy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA., Walter RB; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA.; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98195, USA.; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. |
| Abstrakt: |
Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and improves cure rates. However, it is unclear how best to translate the success of these therapies from B cell malignancies, where use of highly potent immunotherapies is facilitated by identified target antigens with near ubiquitous expression on malignant cells and non-fatal consequences from "on-target, off-tumor cell" toxicities. Herein, we review the current status of CAR-modified IEC therapies for AML, with considerations regarding suitable, relatively leukemia-restricted target antigens, expected toxicities, and interactions of the engineered cells with a profoundly immunosuppressive tumor microenvironment that restricts their therapeutic efficacy. With these challenges in mind, we will discuss possible strategies to improve the cells' potency as well as their therapeutic window for optimal clinical use in AML. |
