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

NCT07743047 | Not Yet Recruiting

• 1 other identifier: SynT
• Study Type: observational
• Target: 65
• Locations: 0 countries
• Sites: N/A

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 pateints 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Identification and functional characterization of novel tumor-specific TCRs

  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.

  From study initiation through month 24

Secondary Outcomes (1)

• Development of therapeutic T-cell circuits and investigation of AML resistance to T-cell-mediated cytotoxicity

  From study initiation through year 5

Study Arms (3)

AML patients

Healthy volunteers

Hematopoietic stem cell transplant donors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will include samples from approximately 30 patients affected by acute myeloid leukemia (AML), including retrospective and prospective bone marrow (BM) and peripheral blood (PB) samples. Retrospective samples consist of BM and PB samples collected since April 2006 and stored in the Hematological Cancer Biobank of the Ospedale San Raffaele, under specific informed consent and in accordance with the objectives of the present study. Prospective samples will consist of additional peripheral blood volumes collected during routine clinical procedures from AML patients after signing study-specific informed consent. The study will also include samples from 25 healthy donors recruited through the agreement between Ospedale San Raffaele and Garbagnate Hospital.

You may qualify if:

• Age ≥18.
• Written informed consents 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/breast-feeding and/or fertile-age female patients are eligible.
• AML diagnosis in case of patients
• Hematopoietic stem cell transplant donors harvested in the OSR biobank
• Patients or healthy donor samples should express the HLA allele(s) of our interest

You may not qualify if:

• Inability to provide a written informed consent.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 3, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: August 3, 2026

Record last verified: 2026-07