Grant Award Details

Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α-hydroxylase for Acute Myeloid Leukemia Therapy
Grant Number: 
DISC1-10620
Project Objective: 
  • This project explores the feasibility of treating acute myeloid leukemia with a combination of 1) 5-Azacytidine chemotherapy, which primes the bone narrow niche and 2) transplantation of autologous HSCs modified to express Vitamin D in the bone marrow niche, thereby promoting terminal differentiation of leukemic stem cells

Investigator: 
Institution: 
Type: 
PI
Disease Focus: 
Acute Myeloid Leukemia
Blood Cancer
Cancer
Human Stem Cell Use: 
Adult Stem Cell
Award Value: 
$178,967
Status: 
Active

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

  • 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