Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Agnieszka Czechowicz, Rahul Palchaudhuri, Amelia Scheck, Yu Hu, Jonathan Hoggatt, Borja Saez, Wendy W. Pang, Michael K. Mansour, Tiffany A. Tate, Yan Yi Chan, Emily Walck, Gerlinde Wernig, Judith A. Shizuru, Florian Winau, David T. Scadden, Derrick J. Rossi

ABSTRACT

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for blood and immune diseases with potential for many settings beyond current standard-of-care. Broad HSCT application is currently precluded largely due to morbidity and mortality associated with genotoxic irradiation or chemotherapy conditioning. Here we show that a single dose of a CD117-antibody-drug-conjugate (CD117-ADC) to saporin leads to > 99% depletion of host HSCs, enabling rapid and efficient donor hematopoietic cell engraftment. Importantly, CD117-ADC selectively targets hematopoietic stem cells yet does not cause clinically significant side-effects. Blood counts and immune cell function are preserved following CD117-ADC treatment, with effective responses by recipients to both viral and fungal challenges. These results suggest that CD117-ADC-mediated HSCT pre-treatment could serve as a non-myeloablative conditioning strategy for the treatment of a wide range of non-malignant and malignant diseases, and might be especially suited to gene therapy and gene editing settings in which preservation of immunity is desired. More... »

PAGES

617

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-08201-x

DOI

http://dx.doi.org/10.1038/s41467-018-08201-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111950381

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30728354


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08201-x'

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-018-08201-x'


 

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