Novel targets and pathways for hematopoiesis and leukemia

Description of the Invention

Although umbilical cord blood (CB)‐derived hematopoietic stem cells (HSCs) are essential in many lifesaving regenerative therapies, their limited number in CB units has significantly restricted their clinical use and the subsequent advantages they provide during transplantation. The achievement of ex vivo expansion of hematopoietic stem and progenitor cell (HSPCs) for the purpose of attaining successful, efficient and event‐free transplantation‐based cell therapies is a sought after goal in the field. Select small molecules that enhance HSPC expansion in culture have been identified that are in preclinical and clinical development, however, in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular pathways that underpin the unique human HSC self‐renewal program could facilitate the development of targeted strategies that expand these critical cell types for regenerative therapies. An understanding of the biology of HSPC expansion will also have an impact in the understanding of leukemia, which appear to have lost control of the critical mechanisms underlying balanced HSC self‐renewal and differentiation.

Dr. Hope’s group have made significant progress in uncovering the molecular mechanisms behind HSC self‐renewal (Rentas et al Nature 2016 and unpublished). This has led to identification of novel targets against known HSC self‐renewal pathways as well as discovery of pathways not previously associated with HSC expansion. Her group have also identified certain natural product compounds, some derived from plants, which increase the self‐renewal and expansion of HSCs.

Potential Applications

Umbilical cord blood (UCB) transplants are life‐saving treatments for patients with bone marrow and blood cancers which would otherwise face a poor prognosis. However, a successful adult transplant can be limited by the number of hematopoietic stem/progenitor cells (HSPC) in a UCB sample. Technologies enabling expansion of HSPCs would have a significant impact on the global cord blood and stem cell transplant industry.

Sector and Products

Cord Blood Expansion for Transplantation; small molecule therapeutics

ecommNovel targets and pathways for hematopoiesis and leukemia