Research team
Applying Logic gating and a novel source of T cells to formulate the next generation of CAR-T cells for leukemia (CCR+CAR-BM-TILs).
Abstract
Acute myeloid leukemia (AML) treatment remains challenging despite therapeutic advances. About 50% of patients in complete remission (CR) will relapse within 5 years after initial diagnosis. In the past decade, chimeric antigen receptor (CAR)-T cell therapy has been very successful in hematological malignancies like B-cell lymphoma. However, in AML, results have been highly unsatisfactory, despite several preclinical and clinical CAR-T studies. Challenges in CAR-T cell therapy for AML include AML heterogeneity, lack of a leukemia-specific antigens leading to off-tumor toxicity, and an immunosuppressive bone marrow (BM) microenvironment. In this PhD project, I aim to investigate and tackle these main problems in AML CAR-T treatment by developing CAR-T cells using BM-derived tumor infiltrating lymphocytes (TILs) as a novel CAR-T-cell source and a logic AND-gated approach with co-stimulatory receptors (CCR) and signaling CARs, generating AND-gated BM-derived CCR+CAR-engineered TILs. For this, I will (1) find a suitable protocol for BM-derived TIL expansion, (2) profile BM-derived TILs of AML patients, (3) find a combination of antigens more specific for AML and not for normal HSCs, using logic AND-gated CAR strategy, and (4) evaluate the antileukemic functionality of AND-gated CCR+CAR-BM-TILs. This project will bring closer a new and potent generation of CAR-T therapies for leukemia.Researcher(s)
- Promoter: Anguille Sébastien
- Co-promoter: Campillo Davó Diana
- Fellow: Katana Zoi
Research team(s)
Project type(s)
- Research Project
Development of a novel chimeric antigen receptor (CAR)-T cell therapy for acute myeloid leukemia.
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)
- Promoter: Anguille Sébastien
- Fellow: Katana Zoi
Research team(s)
Project type(s)
- Research Project