{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:50:30Z","timestamp":1785754230821,"version":"3.56.0"},"reference-count":67,"publisher":"Radiation Research Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2018,5,18]]},"abstract":"<jats:p>BBT-059 is a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic-promoting and anti-apoptotic properties, making it an ideal candidate for further development as a potential radiation medical countermeasure (MCM) for the hematopoietic acute radiation syndrome (H-ARS). The efficacy of BBT-059 has been previously established in an H-ARS murine model and in a nonhuman primate (NHP) model through pharmacokinetic and pharmacodynamic (PK\/PD) studies. In the current study, a total of 12 na\u00efve NHPs (rhesus macaques) were administered a single 37.5 \u00b5g\/kg, 75 \u00b5g\/kg, or 150 \u00b5g\/kg dose of BBT-059 (n = 4 animals per group) subcutaneously and monitored for 21 days post-administration. To further evaluate the safety profile of BBT-059 and better understand its mechanism of action, proteomic analyses were performed to assess the impact of BBT-059 on proteins, pathways, and any dose-dependent differences. Blood samples were collected and serum was isolated and analyzed using trapped ion mobility time-of-flight mass spectrometry (timsTOF-MS). Statistically significant time-dependent changes were present in all dose groups when comparing pre-administration to post-administration samples, peaking around 3 days post-administration and reverting to near-normal levels by the end of the study period. Any dose of BBT-059 triggered a robust, acute-phase proteomic response characterized by an increase in platelet and neutrophil counts, elevated IL-6 expression, and an activation of the neutrophil degranulation and platelet activation, signaling and aggregation pathways. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM.<\/jats:p>","DOI":"10.1667\/rade-25-00170","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:03:31Z","timestamp":1779149011000},"page":"207-220","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Studies in Rhesus Nonhuman Primates Administered a Promising Radiation Medical Countermeasure under Development, BBT-059"],"prefix":"10.1667","volume":"206","author":[{"given":"Alana D.","family":"Carpenter","sequence":"first","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issa Melendez","family":"Miranda","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Petrus","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyalakshmi","family":"Kandhavelu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Y.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluseyi O.","family":"Fatanmi","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Fam","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George N.","family":"Cox","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita K.","family":"Cheema","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"55","doi-asserted-by":"crossref","unstructured":"S Zhou, Y Li, L He, et al.  \"Stem Cell Res Ther.\"  13, \"Haptoglobin is an early indicator of survival after radiation-induced severe injury and bone marrow transplantation in mice.\" 461 (2022)","DOI":"10.1186\/s13287-022-03162-x"},{"key":"61","doi-asserted-by":"crossref","unstructured":"T Tanaka, M Narazaki, T Kishimoto,  \"Cold Spring Harb Perspect Biol.\"  6, \"IL-6 in inflammation, immunity, and disease.\" a016295 (2014)","DOI":"10.1101\/cshperspect.a016295"},{"key":"26","doi-asserted-by":"crossref","unstructured":"AD Carpenter, Y Li, IM Miranda, et al.  \"Radiat Res.\"  203, \"Pharmacokinetic and metabolomic studies with BBT-059 in nonhuman primates exposed to total-body gamma radiation.\" 83 (2025)","DOI":"10.1667\/RADE-24-00219.1"},{"key":"17","doi-asserted-by":"crossref","unstructured":"RP Gale  and JO Armitage  \"Blood Rev.\"  45, \"Use of molecularly-cloned haematopoietic growth factors in persons exposed to acute high-dose, high-dose rate whole-body ionizing radiations.\" 100690 (2020)","DOI":"10.1016\/j.blre.2020.100690"},{"key":"20","doi-asserted-by":"crossref","unstructured":"DI Bunin, J Bakke, CE Green, et al.  \"Int J Radiat Biol.\"  96, \"Romiplostim (Nplate) as an effective radiation countermeasure to improve survival and platelet recovery in mice.\" 145 (2020)","DOI":"10.1080\/09553002.2019.1605465"},{"key":"52","doi-asserted-by":"crossref","unstructured":"M Milacic, D Beavers, P Conley, et al.  \"Nucleic Acids Res.\"  52, \"The reactome pathway knowledgebase 2024.\" D672 (2024)","DOI":"10.1093\/nar\/gkad1025"},{"key":"1","doi-asserted-by":"crossref","unstructured":"AL DiCarlo, MJ Homer, C N Coleman,  \"Journal of Radiol Prot.\"  41, \"United States medical preparedness for nuclear and radiological emergencies.\" 1420 (2021)","DOI":"10.1088\/1361-6498\/ac0d3f"},{"key":"2","doi-asserted-by":"crossref","unstructured":"N Yeddanapudi, MA Clay, DP Durham, et al.  \"Int J Radiat Biol.\"  96, \"Informing CONOPS and medical countermeasure deployment strategies after an improvised nuclear device detonation: the importance of delayed treatment efficacy data.\" 4 (2020)","DOI":"10.1080\/09553002.2018.1532618"},{"key":"4","doi-asserted-by":"crossref","unstructured":"C. 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