Researcher, assistant academic staff - Hematology, Department of Internal Medicine and Pediatrics (Faculty of Medicine and Health Sciences, UGent)
Principal investigator: prof. Tessa Kerre (PhD)
Acute myeloid leukemia (AML) can be cured by chemotherapy in less than half of the patients. Unfortunately, the chance of relapse after chemotherapy is high in AML. Stem cell transplantation can be used to cure patients, but it carries a high risk of toxicities and mortality, especially in older patients with comorbidities. Moreover, a suitable donor can not be found for all patients.
Therefore, we have developed a novel immunotherapeutic strategy in which we generate in vitro T-cells that recognize a known tumor antigen, starting from hematopoietic stem and precursor cells from cord blood or other healthy donor or patient sources (mobilized peripheral blood, leucapheresis, or bone marrow).
An important condition for effective T-cell immunotherapy is the choice of the target tumor antigen. For B-cell malignancies, CD19 has proven to be superior as a target antigen. For AML, we do not have such a target yet. In the past, T-cells recognizing WT1 through their T-cell receptor, have shown to be highly specific, but also have a low affinity due to expression of WT1 on normal cells (albeit at low levels). We are now searching for a novel target antigen that is expressed in both AML blasts and leukemic stem cells (which are deemed responsible for relapse in AML), using multiparameter flow cytometry and bio-informatics (in collaboration with prof. Philippé, and the DaMBi group of prof. Saeys). Chimeric antigen receptors (CARs) can be developed to target surface antigens, and can hopefully be deployed as a new treatment strategy for AML.
- In vitro OP9-DL1 co-culture and subsequent maturation in the presence of IL-21 generates tumor antigen-specific T cells with a favorable less-differentiated phenotype and enhanced functionality. OncoImmunology. 2021
- T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources. OncoImmunology, 2020. (PMID: 32117593)
- In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection'. Leukemia, 2014. (PMID: 24091848)
MRB2, Corneel Heymanslaan 10, 9000 Ghent