ENGRAFTMENT OF STEM CELLS WITH A COMBINATION OF AN AGENT THAT TARGETS STEM CELLS AND MODULATION OF IMMUNOREGULATORY SIGNALING

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present inven...

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Bibliographische Detailangaben
Hauptverfasser:	RING, Aaron Michael, SCHNORR, Peter, WEISSMAN Irving L, WEISKOPF, Kipp Andrew, CHHABRA, Akanksha, SHIZURU, Judith, A
Format:	Patent
Sprache:	eng ; fre ; ger
Schlagworte:	BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS OR TEST PAPERS THEREFOR CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES ENZYMOLOGY HUMAN NECESSITIES HYGIENE MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MUTATION OR GENETIC ENGINEERING ORGANIC CHEMISTRY PEPTIDES PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROCESSES OF PREPARING SUCH COMPOSITIONS SPIRITS VINEGAR WINE
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Beschreibung
Zusammenfassung:	The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.