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| Name | Class |
|---|---|
| University of California, San Diego | OTHER |
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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.
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.
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| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with leukemia and their potential bone marrow donors.
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| Name | Affiliation | Role |
|---|---|---|
| Edward Ball, MD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego | La Jolla | California | 92093 | United States | ||
| Northside Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11719375 | Background | Montagna D, Maccario R, Locatelli F, Rosti V, Yang Y, Farness P, Moretta A, Comoli P, Montini E, Vitiello A. Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy. Blood. 2001 Dec 1;98(12):3359-66. doi: 10.1182/blood.v98.12.3359. | |
| 22934277 | Background |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Samples will be shipped to Persimmune for processing and storage with results shared with Dr. Ball and his lab at UCSD.
| 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 |
| Atlanta |
| Georgia |
| 30342 |
| United States |
| Kreiter S, Castle JC, Tureci O, Sahin U. Targeting the tumor mutanome for personalized vaccination therapy. Oncoimmunology. 2012 Aug 1;1(5):768-769. doi: 10.4161/onci.19727. |
| 23090074 | Background | Klebanoff CA, Gattinoni L, Restifo NP. Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy? J Immunother. 2012 Nov-Dec;35(9):651-60. doi: 10.1097/CJI.0b013e31827806e6. |
| 23059871 | Background | Brenner MK. Will T-cell therapy for cancer ever be a standard of care? Cancer Gene Ther. 2012 Dec;19(12):818-21. doi: 10.1038/cgt.2012.74. Epub 2012 Oct 12. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |