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Cancer research

Gene Therapy Breakthrough: Researchers Develop New Strategy for Engraftment in Monogenetic Disorders

Strategic Insights

— 1 min read

A groundbreaking new study published in Blood Advances has made significant strides in gene therapy, particularly in the treatment of monogenetic disorders such as hemoglobinopathies and lysosomal storage diseases. A team of researchers from the Fred Hutchinson Cancer Research Center has developed a novel strategy to maintain engraftment levels in patients undergoing cell and gene therapies. The study, titled "Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques," demonstrates a proof-of-concept and safety of an epitope editing-based enrichment/protection strategy in macaques.

Key Takeaways:

  • Researchers from the Fred Hutchinson Cancer Research Center developed a new strategy to maintain engraftment levels in patients undergoing cell and gene therapies.
  • The study focused on CD33, a protein expressed early on hematopoietic stem and progenitor cells, and demonstrated a proof-of-concept and safety of an epitope editing-based enrichment/protection strategy.
  • The research used CRISPR/CRISPR-associated protein 9 or adenine base editor to ablate CD33 in rhesus macaques, showing similar post-transplant recovery kinetics and equivalent levels of engraftment.
  • A V-set domain-specific CAR construct (CAR33) was created and validated in vitro, and treated both animals with autologous CAR33 T cells, causing specific depletion of CD33WT but not CD33null progeny.
  • The study demonstrated a transient enrichment for gene-edited cells in the blood, with no depletion seen in the bone marrow stem cell compartment.

Statistics:

  • The study demonstrated a proof-of-concept and safety of an epitope editing-based enrichment/protection strategy in macaques.
  • The research showed similar post-transplant recovery kinetics and equivalent levels of engraftment in rhesus macaques edited with either CRISPR/CRISPR-associated protein 9 or adenine base editor.
  • The V-set domain-specific CAR construct (CAR33) was validated in vitro and demonstrated specific depletion of CD33WT but not CD33null progeny.
  • The study demonstrated a transient enrichment for gene-edited cells in the blood, with no depletion seen in the bone marrow stem cell compartment.

Sources:

  • Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques. Blood Advances, 2025,9(10):2367-2378. The publisher for Blood Advances is Elsevier.
  • doi-org.sdpl.idm.oclc.org/10.1182/bloodadvances.2024015016
  • NewsRx. Research on Gene Therapy Detailed by Researchers at Fred Hutchinson Cancer Research Center (Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques). Hematology Week. May 26, 2025; p 91.

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