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Cancer

Breakthrough in Cancer Gene Therapy: Multiplex Base Editing Showcases Promise

Strategic Insights

— 1 min read

Researchers at Columbia University Irving Medical Center have made a significant advancement in cancer gene therapy by developing a multiplex base editing approach. This innovative method involves editing the CD33 gene to protect myeloid progeny from cancer therapies while preserving normal hematopoiesis. The study demonstrates the potential for improved immunotherapies with reduced off-leukemia toxicity. Furthermore, the researchers successfully performed multiplexed adenine base editing of the CD33 and gamma globin genes, achieving long-term persistence of dual gene-edited cells with HbF reactivation in nonhuman primates.

Key Takeaways:

  • The study focuses on developing a method to spare on-target toxicity to normal cells in genetically engineered immune or hematopoietic cells.
  • The researchers developed a base editing approach exploiting a naturally occurring CD33 single nucleotide polymorphism, leading to removal of full-length CD33 surface expression on edited cells.
  • The CD33 editing protected myeloid progeny from CD33-targeted therapeutics without affecting normal hematopoiesis in vivo.
  • The study demonstrates potential for improved immunotherapies with reduced off-leukemia toxicity.
  • The researchers achieved highly efficient (70%) multiplexed adenine base editing of the CD33 and gamma globin genes, resulting in long-term persistence of dual gene-edited cells with HbF reactivation in nonhuman primates.
  • The use of the CD33 antibody-drug conjugate Gemtuzumab Ozogamicin showed resistance of engrafted, multiplex edited human cells in vivo, and a 2-fold enrichment for edited cells in vitro.
  • The study highlights the potential of adenine base editors for improved immune and gene therapies.

Statistics:

  • 70% efficiency in multiplexed adenine base editing of the CD33 and gamma globin genes.
  • Success in long-term persistence of dual gene-edited cells with HbF reactivation in nonhuman primates.
  • 2-fold enrichment for edited cells in vitro.
  • CD33 editing protected myeloid progeny from CD33-targeted therapeutics in vivo.
  • Improved immunotherapies with reduced off-leukemia toxicity demonstrated.

Sources:

  • "Multiplex base editing to protect from CD33 directed drugs for immune and gene therapy." Nature Communications, 2025,16(1):1-17. (Nature Communications - https://www.nature.com/ncomms/.)
  • NewsRx. New Cancer Gene Therapy Findings from Columbia University Irving Medical Center Described (Multiplex base editing to protect from CD33 directed drugs for immune and gene therapy). Hematology Week. June 16, 2025; p 18.

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