Granulocyte/Monocyte Precursors to Treat Neutropenia after Cancer Chemotherapy

PROJECT SUMMARY ABSTRACT The objective of this proposal is to move our product forward toward commercialization by improving the quality of life for breast cancer chemotherapy patientsThis will be achieved by the following Specific AimsAimwill optimize differentiation of GMPs and neutrophil lineages in culture in response to G CSFThis will be assessed by flow cytometry to quantify production of neutrophil lineages and by colony forming assays to quantify lineage multipotencyAimwill identify the optimal extent of lineage differentiation for production of GMPs and neutrophil lineages to prevent neutropenia in the busulfan cancer chemotherapy treatment of NSG miceEfficacy will be quantified by production of human cells in peripheral bloodbone marrow and spleen using flow cytometryThese studies will define the process to manufacture a frozenoff the shelf product to directly transfuse into chemotherapy patients at increased risk of infectionThe significance of our proposal is based on the strong scientific premise of extensive literature and our preliminary dataOur finding has the potential to revolutionize the value of CB stem cells in transplant indications by filling the unmet clinical need for more cord blood derived cellsThe need for more cells has long been extolled but ex vivo manipulations have only brought incremental improvementsOur technology provides unprecedented numbers of stemprogenitor and immune cells to patient quality of life at a remarkably reduced cost from scale up manufacturingThe proposed studies will leverage this next generation expansion discovery to address the problem of reduction of GMPs after chemotherapyneutropeniaand consequent increases in infectionThisin turnis a significant problem because infections compromise maintenance of chemotherapy regimensthus resulting in poorer outcomesFurtherthe proposed studies embody a rigorous scientific approach based on state of the art literatureThis innovation is truly a paradigm shift because previously the limited numbers of CB cells has limited this valuableefficacious cellular therapy from impacting larger numbers of patientsThis work will complete preclinicalin vivoproof of principle studies in miceIf successfulthis will have a major impact on chemotherapy patients by leading to a reduction in Ainfections that compromise maintenance of the chemotherapy regimen in these patientsBhospitalization timesCcostand Dmorbidity and mortalityUltimatelythe proposed studies will accelerate Cord Blood PlusInccloser to migration to cGMP productiona pre IND meeting with the FDAand design of a protocol for a Phasesafety and tolerability clinical trial through our new collaboration between MD Anderson Cancer Center and UTMB PROJECT NARRATIVE Cord blood stem cells are used to treat patients who have compromised bone marrow from cancer chemotherapy or radiation therapy but the limited numbers of cells has limited successThis proposal utilizes a novel method for unprecedented expansion of cord blood stemprogenitorand hematopoietic cells to develop the next generation of cord blood stem cell therapy products to produce human GMPs and neutrophil lineages that produce neutrophils responsible for reducing infectionsThe outcome of this work will use this optimal product in the design of a Phasesafety and tolerability study in cancer chemotherapy patients by Cord Blood PlusIncwith our partners at MD Anderson Cancer Center in Houston