Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α-hydroxylase for Acute Myeloid Leukemia Therapy
Grant Award Details
Grant Type:
Grant Number:
DISC1-10620
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$178,967
Status:
Closed
Progress Reports
Reporting Period:
Year 1
Grant Application Details
Application Title:
Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α-hydroxylase for Acute Myeloid Leukemia Therapy
Public Abstract:
Research Objective
We propose a new approach to differentiation therapy for acute myeloid leukemia by producing local level of high-dose vitamin D in bone marrow via cell therapy with engineered hematopoietic stem cells
Impact
If proven successful, the proposed research can serve as a major breakthrough in the treatment of multiple subtypes of AML and particularly important for improving survival in older patients.
Major Proposed Activities
We propose a new approach to differentiation therapy for acute myeloid leukemia by producing local level of high-dose vitamin D in bone marrow via cell therapy with engineered hematopoietic stem cells
Impact
If proven successful, the proposed research can serve as a major breakthrough in the treatment of multiple subtypes of AML and particularly important for improving survival in older patients.
Major Proposed Activities
- Evaluate homing and expansion of engineered hematopoietic stem cells in bone marrow of human leukemic xenograft (HLX) mice after precondition with 5-Azacytidine
- Optimize the number of injected hematopoietic stem cells without causing hypercalcemia
- Determine if the local concentration of vitamin D3 is sufficient to differentiate leukemic blasts in bone marrow
- Determine the efficacy of combination therapy of 5-Azacytidine and cell therapy by measuring overall survival
- Determine the efficacy of combination therapy of 5-Azacytidine and cell therapy by measuring leukemia burden
- Monitor serum calcium level from peripheral blood during treatment period
Statement of Benefit to California:
Acute myeloid leukemia (AML) has poor outcome, especially in older, ailing patients who can't tolerate aggressive conventional chemotherapy. If proven successful, our work can serve as a major breakthrough in the treatment of multiple subtypes of AML and particularly important for improving survival in older patients. The State of California will be a leading authority in this field. Further, this work will benefit patients around the world, not limited citizens of California
