Samples From Leukemia Patients and Their Donors to Identify Specific Antigens

Study Overview
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Brief Summary
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The purpose of this project is to develop a process to identify highly personalized antigens that are uniquely expressed by the patient's own leukemia cells that can be used for cellular immune therapy.

Detailed Description
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It is well known that tumor cells and leukemia cells express different surface structures (called antigens) that can serve as targets for cancer cell destruction by the immune system. Effective immune therapies are characterized by high specificity and low toxicity. One of the major obstacles impeding the use of these therapies as standard of care is the identification of good target antigens. In acute myeloid leukemia (AML) there is major patient to patient variation in leukemia antigens, so there is no universal AML cell target. Rather, each patient has a unique array of potential cell targets. Thanks to the rapid progress of new DNA/RNA sequencing technologies, the identification of these unique, patient-specific leukemia cell antigen-targets is now possible. The purpose of this project is to develop a process to identify highly personalized antigens that are uniquely expressed by the patient's own leukemia cells that can be used for cellular immune therapy.

Official Title
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Bone Marrow and Peripheral Blood (PB) Samples From Patients With Leukemia and PB From Their BM Donors (BMD) to Identify Leukemia-Specific Antigens (LSA) and Graft Versus Host Disease Antigens (GVHDA) for Use in Cellular Immunotherapy

Conditions
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Acute Myeloid Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AML with plan to receive a bone marrow transplant Exclusion Criteria: NA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genomics of patients with leukemia and their HLA matched bone marrow transplant donors. | To sequence the exome and transcriptome obtained from leukemia cells and the exome from their lymphocytes, and the lymphocytes from their HLA matched marrow transplant donors. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of patients' leukemia cell mutations and polymorphisms that are different from their HLA matched bone marrow transplant donors | To select leukemia specific mutations (aka, variants), ie those that are different from both the patient's non-leukemic cells and their HLA matched marrow transplant donor's immune cells by comparing Leukemia cell, Patient normal cell, and Donor exome sequences. | 5 years | 
| Immunogenic mutant neoantigen peptide selection | To select peptides that represent the sequences obtained from Aim 2, according to their ability to bind to the identical patient/donor T cell major histocompatibility receptors. | 5 years | 
| Peptide immunogenicity confirmation and donor T cell stimulation | To test the peptides from Aim 3 for their in vitro immunogenicity for T lymphocytes obtained from the donor. | 5 years | 
| Data analysis and interpretation | To create and analyze a database summarizing the data obtained from Aims 1-4 for the purpose of IND submission and clinical trial design. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Leukemia, Acute Myeloid Leukemia, AML