Optimized use of UM171 and derived molecules for the next generation of genetically engineered blood stem cell grafts in high-risk leukemia therapy.

Hematopoietic stem cells (HSCs) have the ability to reconstitute hematopoiesis by giving rise to all blood lineages without exhaustion. Despite the widespread clinical application of HSCs, the success of HSC transplantations relies mainly on the availability of suitable donors and adequate grafts. Obtaining high-quantity and quality hematopoietic grafts for curing hematological and non-hematological diseases remains still challenging. We have previously reported that the small compound UM171 stimulates the expansion of functional long-term HSCs and also contributes on expanding immuno-modulatory cells. The recent knowledge on the UM171 mechanism of action will allow us to further improve the HSCs expansion conditions and to evaluate new analogs of UM171 for their improved properties. Defining optimal expansion conditions for HSCs will provide the milestone to further genetically engineer these cells and offer alternative therapies to patients. For instance, production of CAR expressing effector cells will provide an improved approach with the potential to treat acute myeloid leukemia. Thus, this proposal seeks to better understand the factors influencing ex vivo HSC culture and support the development of engineered HSC grafts via our expertise and of ExCellThera’s expansion and cell engineering platform.

Faculty Supervisor:

Guy Sauvageau

Student:

Partner:

ExCellThera

Discipline:

Life Sciences

Sector:

Agriculture; Health and Related Sciences & Technology; Professional, scientific and technical services

University:

Université de Montréal

Program: