Astatine 211-based conditioning with a humanized CD45 antibody for autologous hematopoietic stem cell gene therapy.

-based CD45 radioimmunotherapy achieves effective, targeted conditioning with minimal non-hematologic toxicity in primates, enabling high-efficiency gene-edited HSPC engraftment.

• Why it matters: Current conditioning regimens for autologous HSPC transplantation cause significant non-hematologic toxicities, limiting their safety and applicability. Developing targeted, less toxic alternatives is crucial for advancing gene therapy.
• What they did: Researchers used a humanized CD45 antibody labeled with astatine-211 to deliver targeted radiation in nonhuman primates, combined with multiplex gene editing of HSPCs and detailed single-cell sequencing to assess engraftment and lineage contribution.
• The result: The approach resulted in dose-dependent, stable engraftment of gene-edited cells with up to 70% editing efficiency, complete marrow replacement, and long-term persistence (>18 months), demonstrating a promising targeted conditioning strategy.