HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8–9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit–expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD50/30) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12–14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting hematopoiesis and recovery of immune functions and possibly gastrointestinal functions, likely through a network of interactions involving dendritic cells, osteoblasts, and soluble factors such as IL-12, IFN-γ, and cytoprotectant erythropoietin

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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DILUTED ACID PRETREATMENT OF PINUS RADIATA FOR BIOETHANOL PRODUCTION USING IMMOBILIZED SACCHAROMYCES CEREVISIAE IR2-9 IN A SIMULTANEOUS SACCHARIFICATION AND FERMENTATION PROCESS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The production of bioethanol from pretreated lignocellulosic materials requires the utilization of microorganisms adapted to ferment the materials in conditions were high consistency, temperatures and inhibitors concentrations were commonly found. The yeast immobilization in calcium alginate capsules has been reported to enhance the yeast protection and increase the efficiency in the fermentation process. In this work, it was investigated the use Saccharomyces cerevisiae immobilized in calcium alginate and its performance in simultaneous saccharification and fermentation (SSF) of diluted-acid-pretreated Pinus radiata. Results showed that when immobilized yeast was used, the bioethanol yield from pretreated wood was higher than with free yeast cells during a SSF process. Maximum ethanol yield obtained from the acid pretreated and milled wood chips was 153 L/ton wood, while from the hydrolysate fraction it was 18 L/ton wood. The sum of ethanol produced from dilute acid pretreated P. radiata for both solid and liquid fractions was 171 L ethanol/ton wood from a maximum theoretical of 236 L/ton pretretated wood (or 72% of conversion).564901906Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1070492]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)SENACYT-IFARHU, PanamaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1070492