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Bone Marrow Transplant. 2015 Jul;50(7):924-30. doi: 10.1038/bmt.2015.74. Epub 2015 Apr 27.

Efficacy and safety of CDX-301, recombinant human Flt3L, at expanding dendritic cells and hematopoietic stem cells in healthy human volunteers.

Author information

1
1] The Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, USA [2] Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
The Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, USA.
3
Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.
4
Celldex Therapeutics, Inc., Needham, MA, USA.

Abstract

Fms-like tyrosine kinase-3 ligand (Flt3L) uniquely binds the Flt3 (CD135) receptor expressed on hematopoietic stem cells (HSCs), early progenitor cells, immature thymocytes and steady-state dendritic cells (DCs) and induces their proliferation, differentiation, development and mobilization in the bone marrow, peripheral blood and lymphoid organs. CDX-301 has an identical amino-acid sequence and comparable biological activity to the previously tested rhuFlt3L, which ceased clinical development over a decade ago. This Phase 1 trial assessed the safety, pharmacokinetic, pharmacodynamic and immunologic profile of CDX-301, explored alternate dosing regimens and examined the impact of rhuFlt3L on key immune cell subsets. Thirty healthy volunteers received CDX-301 (1-75 μg/kg/day) over 5-10 days. One event of Grade 3 community-acquired pneumonia occurred. There were no other infections, dose-limiting toxicities or serious adverse events. CDX-301 resulted in effective peripheral expansion of monocytes, hematopoietic stem and progenitor cells and key subsets of myeloid DCs and plasmacytoid DCs, with no clear effect on regulatory T cells. These data from healthy volunteers support the potential for CDX-301, as monotherapy or in combination with other agents, in various indications including allogeneic HSC transplantation and immunotherapy, but the effects of CDX-301 will need to be investigated in each of these patient populations.

PMID:
25915810
PMCID:
PMC4532305
DOI:
10.1038/bmt.2015.74
[Indexed for MEDLINE]
Free PMC Article

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