Harnessing the Immunosuppressive Leukemic Microenvironment to Engineer T Cells With Enhanced Anti-tumor Functionality (SynT)

This is a monocentric, retrospective and prospective study aimed to underline the potential of T-cell receptor (TCR)-mediated Ab recognition from the post transplant setting in acute myeloid leukemia (AML). The study is based on three key biological concepts:

• the essential role of CD4+ T cells in leukemia immunosurveillance,
• the impact of human leukocyte antigen (HLA) loss or downregulation on immune escape,
• the ability of leukemic cells to remodel the tumor microenvironment and impair T-cell function.

By addressing these mechanisms, the study aims to identify novel TCRs and generate next-generation engineered T-cell products with improved anti-leukemic activity. The study will be conducted using samples from healthy donors and patients with AML.

The Retrospective part will involve samples collected per standard of care from patients already present in the institutional Hematologic Cancer Biobank, while prospective part will regard the use of samples collected during the study protocol from healthy donor and AML patients. Healthy donor peripheral blood samples will be used to isolate tumor-specific TCRs and generate engineered T cells, whereas bone marrow and peripheral blood samples from AML patients will be used to evaluate the anti-tumor activity of the engineered T cells.