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• W2554344438 abstract "Abstract hLF1-11, comprising the N-terminal 11 AA of the human lactoferrin protein, has previously been shown to have a broad antimicrobial spectrum. The efficacy towards several strains of bacteria and fungi was demonstrated in in vitro and in vivo models. At this moment, hLF1-11 is in clinical development for use as broad spectrum anti-fungal and anti-bacterial prophylaxis in hematopoetic stem cell transplantation (HSCT) patients. There is data to support that the hLF1-11 mechanism of action is not restricted to direct killing of the pathogen, but that the indirect, immune modulatory and immune activating properties are important for hLF1-11 efficacy in vivo at low doses. In earlier studies, efficacy of hLF1-11 was shown in neutropenic animals systemically infected with Candida albicans. In the present studies antimicrobial efficacy and safety of hLF1-11 was tested in animal models that resemble the immune compromised state of HSCT patients shortly after transplantation. In cyclophosphamid and cyclosporin treated animals, hLF1-11 significantly reduced intra muscular infection with methicillin resistant Staphylococcus aureus (MRSA) when injected 24 hours after infection. In the same model hLF1-11 showed prophylactic properties in that it was effective even when administered as a single injection 24 hours before local infection with MRSA. In order to assess drug-drug interactions of hLF1-11 with common antibiotics, hLF1-11 was co administered with either vancomycin or ciprofloxacin in the local MRSA infection. Data from these models show that hLF1-11 is effective in combination with standard antibiotic and immunosuppressive care in a HSCT setting. Moreover, the hLF1-11 peptide does not inhibit antibiotic activity of currently used antibiotics. Besides these preclinical safety data, clinical safety was evaluated in a single and multiple ascending dose study in human volunteers. During these studies pharmacokinetic and pharmacodynamic parameters were measured and no drug related adverse effects were observed. Now, preparations are made to evaluate safety and efficacy of hLF1-11 in autologous and allogenic HSCT patients as anti-fungal and anti-bacterial prophylaxis. In conclusion, hLF1-11 is a promising peptide to prevent and treat opportunistic infections in HSCT patients and other immune suppressed patient populations." @default.
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• W2554344438 date "2005-11-16" @default.
• W2554344438 modified "2023-10-16" @default.
• W2554344438 title "The Peptide hLF1-11 as Broad Spectrum Antmicrobial Prophylaxis in HSCT Patients." @default.
• W2554344438 doi "https://doi.org/10.1182/blood.v106.11.3241.3241" @default.
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