Purification of Human Hematopoietic Stem Cells (HSCs) for Clinical Stem Cell Transplantation
Grant Award Details
Grant Type:
Grant Number:
TRAN4-16091
Investigator(s):
Award Value:
$1,499,683
Status:
Pre-Active
Grant Application Details
Application Title:
Purification of Human Hematopoietic Stem Cells (HSCs) for Clinical Stem Cell Transplantation
Public Abstract:
Translational Candidate
Two new monoclonal antibodies anti-CD34 and anti-CD90, and protocols to purify cancer-free and/or T cell free human HSC for clinical transplantation.
Area of Impact
The development of hematopoietic stem cell-based therapies, starting with rescue of metastatic breast cancer patients with their own cancer-free HSC
Mechanism of Action
The mechanism is using highly purified HSC to regenerate the blood and immune systems without contaminant disease-causing cells. For cancer patients who undergo transplantation with their own stem cells, harvesting stem cells from blood may also collect circulating cancer cells. We propose to add a step of purification to current HSC enrichment protocols. We’ll develop specific reagents and cell sorting protocols to yield cancer-free human HSCs for a safer clinical transplantation.
Unmet Medical Need
Current transplantations of blood-forming cells are hindered by the presence of contaminating cells; mobilized blood and CD34 selected cells from women with MBC have cancer cells in the grafts. Pure CD34+90+ HSCs rescue patients from HDCT, lack cancer cells, and prolong survival in about 66% of patients, and cure 33%, otherwise incurable. Purified HSC lack donor T cells and can induce transplantation tolerance to HSC donor organs or tissue stem cell transplant without graft vs host disease.
Project Objective
Producing reagents and protocols for HSC isolation
Major Proposed Activities
Two new monoclonal antibodies anti-CD34 and anti-CD90, and protocols to purify cancer-free and/or T cell free human HSC for clinical transplantation.
Area of Impact
The development of hematopoietic stem cell-based therapies, starting with rescue of metastatic breast cancer patients with their own cancer-free HSC
Mechanism of Action
The mechanism is using highly purified HSC to regenerate the blood and immune systems without contaminant disease-causing cells. For cancer patients who undergo transplantation with their own stem cells, harvesting stem cells from blood may also collect circulating cancer cells. We propose to add a step of purification to current HSC enrichment protocols. We’ll develop specific reagents and cell sorting protocols to yield cancer-free human HSCs for a safer clinical transplantation.
Unmet Medical Need
Current transplantations of blood-forming cells are hindered by the presence of contaminating cells; mobilized blood and CD34 selected cells from women with MBC have cancer cells in the grafts. Pure CD34+90+ HSCs rescue patients from HDCT, lack cancer cells, and prolong survival in about 66% of patients, and cure 33%, otherwise incurable. Purified HSC lack donor T cells and can induce transplantation tolerance to HSC donor organs or tissue stem cell transplant without graft vs host disease.
Project Objective
Producing reagents and protocols for HSC isolation
Major Proposed Activities
- Antibody production and validation to generate the reagents for clinical isolation of human HSCs.
- Process development: we’ll test and optimize HSC isolation protocols on every clinical sorting platform available to date.
- Quality assurance: we will develop the tools to assess the yield of purified HSCs, cell viability, purity, and biological function.
Statement of Benefit to California:
We propose to generate and provide reagents for HSC purification in non-profit settings for academic transplantation units, and free for underserved patient populations. Our aim is to be the driver to expand the use of pure HSC isolation and transplantation for a variety of human diseases, beginning with metastatic breast cancer. California residents who can benefit medically will have the first access to these investigational therapies which we hope will be implemented world-wide.