Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats.
| Autor: | Peterson R; Helaina Inc., New York, NY, USA., Crawford RB; Michigan State University, East Lansing, MI, USA., Blevins LK; Michigan State University, East Lansing, MI, USA., Kaminski NE; Michigan State University, East Lansing, MI, USA., Clark AJ; Helaina Inc., New York, NY, USA., Malinczak CA; Helaina Inc., New York, NY, USA. |
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| Jazyk: | angličtina |
| Zdroj: | International journal of toxicology [Int J Toxicol] 2024 Nov 13, pp. 10915818241299344. Date of Electronic Publication: 2024 Nov 13. |
| DOI: | 10.1177/10915818241299344 |
| Abstrakt: | Oral toxicity and toxicokinetic properties of human lactoferrin (LF) alpha produced in Komagataella phaffii (effera™) were investigated in adult Sprague-Dawley rats over a 28-day period under good laboratory practice conditions. Main study dosing used groups of 10 rats/sex/dose, and a secondary study evaluating toxicokinetic parameters used 6 rats/sex/dose. The vehicle control group received sodium citrate buffer, test groups received daily doses of 200, 600, and 2000 mg of effera™ per kg body weight, and the comparative control group received 2000 mg bovine LF (bLF)/kg body weight per day. T-cell-dependent antibody response against keyhole limpet hemocyanin and immunophenotyping of the spleen were performed as measures of immunotoxicity. Clinical observations, body weight, hematology, coagulation, clinical chemistry, urinalysis, immunotoxicity, gross necropsy, and histopathology were assessed. Toxicokinetic parameters were analyzed as an indication of LF bioavailability, and anti-LF antibody assays were conducted to detect antibodies produced against LF to measure immunogenicity. No treatment related toxicologically significant changes were observed. Based on the absence of toxicologically relevant changes, effera™ is well tolerated in rats at doses up to 2000 mg rhLF/kg/day, an amount ∼400 times that of the estimated daily intake at the 90th percentile proposed for human adult use. Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Authors RP, AJC, and C-AM are all employees of Helaina, Inc. Author NEK is a paid consultant of Helaina, Inc. |
| Databáze: | MEDLINE |
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