Format

Send to

Choose Destination
  • Showing results for a modified search because your search retrieved no results.
Health Phys. 2018 Jul;115(1):65-76. doi: 10.1097/HP.0000000000000841.

PEGylated IL-11 (BBT-059): A Novel Radiation Countermeasure for Hematopoietic Acute Radiation Syndrome.

Author information

1
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Av., Bethesda, MD 20889.
2
Bolder Biotechnology, 2425 55th St., Suite 201, Boulder, CO 80301.

Abstract

Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin-11. A single dose of 1.2 mg kg of BBT-059, administered subcutaneously to CD2F1 mice (12-14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to Co gamma total-body irradiation. A single dose of 0.3 mg kg, administered either 24 h pre-, 4 h post-, or 24 h postirradiation increased the survival of mice to 70-100% from lethal doses of radiation. Preadministration (-24 h) of the drug conferred a significantly (p < 0.05) higher survival compared to 24 h post-total-body irradiation. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pretreated with BBT-059. The drug also increased bone marrow cellularity and megakaryocytes and accelerated multilineage hematopoietic recovery. In addition, BBT-059 inhibited the induction of radiation-induced hematopoietic biomarkers, thrombopoietin, erythropoietin, and Flt-3 ligand. These results indicate that BBT-059 is a promising radiation countermeasure, demonstrating its potential to be used both pre- and postirradiation for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.

PMID:
29787432
PMCID:
PMC5967654
[Available on 2019-07-01]
DOI:
10.1097/HP.0000000000000841
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center