Harnessing the Immunosuppressive Leukemic Microenvironment to Engineer T Cells With Enhanced Anti-tumor Functionality
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- IRCCS San Raffaele
- Enrollment
- 65
- Primary Endpoint
- Identification and functional characterization of novel tumor-specific TCRs
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age ≥18 years
- •Written informed consent to the regulation of Hematologic Cancer Biobank (EmaBank) of the San Raffaele Hospital (retrospective patients) and to the present study protocol (prospective patients or hematopoietic stem cell transplant donors harvested in the OSR biobank )
- •Pregnant or breastfeeding and/or women of childbearing potential are eligible
- •Diagnosis of AML (for patient participants)
- •Hematopoietic stem cell transplant donors whose samples are stored in the OSR Biobank
- •Patients or healthy donor should express the HLA allele(s) of interest
Exclusion Criteria
- •1. Inability to provide a written informed consent.
Arms & Interventions
AML patients
Healthy volunteers
Hematopoietic stem cell transplant donors
Outcomes
Primary Outcomes
Identification and functional characterization of novel tumor-specific TCRs
Time Frame: From study initiation through month 24
Isolation of novel T-cell receptors (TCRs) and evaluation of the efficacy and safety of TCR-engineered T cells specific for HLA class II-restricted peptides through in vitro and in vivo studies. Efficacy will be assessed by antitumor activity and functional characterization, while safety will be evaluated through in vitro assays to identify potential off-target effects and other safety-related parameters.
Secondary Outcomes
- Development of therapeutic T-cell circuits and investigation of AML resistance to T-cell-mediated cytotoxicity(From study initiation through year 5)
Investigators
Eliana Ruggiero
Dr.
IRCCS San Raffaele