ArticleBlood immunology & cellular therapy2025
Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning.
Article in Blood immunology & cellular therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Preventing graft re-JAK-tion: safer transplant conditioning enables murine islet allograft tolerance and diabetes reversal.The Journal of clinical investigation · 2026Article
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- Hematopoietic stem cell therapy with gene modification to treat sickle cell disease.Stem cells translational medicine · 2025Review
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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6 authors.
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Abstract
Hematopoietic stem cell transplantation (HSCT) conditioning using antibody-drug conjugates (ADC) is a promising approach to preparing patients for transplant, potentially avoiding the severe toxicities of conventional chemotherapy- and irradiation-based conditioning regimens. The toxic payload determines the efficacy and potential toxicities of an ADC, but comparison of different payloads in conjugates designed for HSCT conditioning has not been reported. Such comparisons would be greatly facilitated by methods enabling efficient screening of many combinations of antibody and payload. Herein, we used Click chemistry to conjugate four different small molecule payloads to a streptavidin backbone, yielding streptavidin-drug conjugates that can be combined with any biotinylated antibody to rapidly and cost-effectively produce an ADC. We vetted this system by evaluating CD45-targeted ADCs, finding pyrrolobenzodiazepine (PBD) dimers to be the most effective payload of those we tested for targeting mouse and human hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML) cells. Single-dose murine CD45-PBD enabled near-complete conversion to donor hematopoiesis in syngeneic HSCT models as well as in autologous transplantation using gene-edited HSCs. Finally, human CD45-PBD targeted human HSCs
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