Abstract
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of certain hematologic cancers. In this immunotherapy, the patient's T-cells are "armoured" ex vivo with a CAR that targets certain antigens on the tumor cell surface. Once administered, the CAR-T-cells will recognize the tumor cells and mediate lysis of the cells However, CAR-T-cell therapy is not yet a breakthrough for acute myeloid leukemia (AML), a highly aggressive blood cancer with dismal prognosis, due to various reasons. One of the reasons is the lack of a suitable CAR-target antigen on the AML cell surface. Another contributing factor is that the T-cells in AML, which are usually taken from peripheral blood, are deemed suboptimal. It is possible that tumor-infiltrating lymphocytes (or TIL) represent a superior cell population, but little research in the CAR therapy field is focused on TIL. To our knowledge, no research has been conducted on the use of TIL for the development of CAR-T cell therapy in AML. The aim of this project is twofold, with the ultimate goal of developing a new CAR-T-cell therapy for AML. Firstly, in this project, a new CAR targeting a promising target antigen that is highly expressed on the AML cell surface will be tested. Secondly, we wish to determine whether bone marrow-derived TIL may be suitable as a source for CAR-based therapy for AML. In a model of AML, we will perform an extensive phenotypic, transcriptional, and functional characterization of anti-AML CAR-engineered TIL compared to conventional peripheral blood lymphocytes.
Researcher(s)
Research team(s)
Project type(s)