Selection and Use of Hematopoietic Stem Cells for Cell Transplantation and Gene Therapy Approaches

Technology Overview

Hematopoietic stem cells (HSC) are the preferred target population for ex vivo gene therapy with applications ranging from rare monogenetic diseases to HIV. Currently, HSCs are isolated by the marker CD34. However, use of this population has several limitations. Fred Hutch researchers have identified a unique combination of genetic markers (CD90 positive and CD45RA negative) that defines a small subset within the CD34-expressing population, which represents HSCs with self-renewing capacity, multilineage potential, long-term engraftment capability and is conserved between human and nonhuman primates. They have also developed anti-CD90 antibodies and binding fragments that can be used to isolate or target HSCs and MSCs in-vivo or ex-vivo for research, diagnostic and therapeutic purposes and enhance the cell specificity of viral vector-based gene delivery. These methods and tools to isolate, expand, and manipulate HSCs has dramatic potential to reduce the cost of goods for manufacturing of gene and cell therapies and provides a quantitative measure of graft potency.

Applications

•      Selection of HSCs for autologous transplantation  
•      Isolation of HSCs for engineering gene and cell based therapies  

Advantages

•      Predictability that isolated cell population will engraft in vivo in vivo
•      Self-renewal and multi-lineage potential of HSCs  
•      20-fold reduced vector requirements for gene manipulation  

Patent Information

• 16-070: EP3471743A; US-CNT filed,publication pending. 21-116: WO2023196742A1 

Market Overview

• Over 40 million people globally are suffering from hematopoietic diseases and HSC transplantation (HSCT) is an attractive approach for curative treatment. From 2016 to 2020, there were over 100,000 HSC transplants performed in the US (CIBMTR estimates). While HSCTs are on the rise, the use of gene therapy HSC strategies is limited due to barriers in manufacturing associated with the significant cost of clinical grade vectors and reagents. These identified HSC populations would allow for more predictable results of HSCT and also reduce vector and reagent requirements given the fewer cell numbers required for predictable long-term multi-lineage engraftment.

Investigator Overview

• Hans-Peter Kiem, MD - Translational Science and Therapeutics Division, Stephanus Family Endowed Chair for Cell and Gene Therapy