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.
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.
Study Type
OBSERVATIONAL
Enrollment
50
University of California San Diego
La Jolla, California, United States
Northside Hospital
Atlanta, Georgia, United States
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.
Time frame: 5 years
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 5 years
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