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Iranian Journal of Biotechnology، جلد ۲۳، شماره ۲، صفحات ۴۰-۴۸
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عنوان انگلیسی Evaluation of the Safety of A Novel Anti-HER2 Immunotoxin Containing Modified Fragment of Pseudomonas Exotoxin in BALB/C Mice
چکیده انگلیسی مقاله Background:
Human epidermal growth factor-2 (HER-2) receptors are overexpressed in some malignancies like breast cancer. Previously, we constructed a novel anti-HER immunotoxin, scFv-PE35KDEL, containing modified fragments of Pseudomonas exotoxin, which showed remarkable in vitro cytotoxicity against breast cancer cells. In vivo safety evaluation is essential for evaluating toxicity to perform in vivo efficacy studies. This study aimed to evaluate the acut toxicity of scFv-PE35KDEL in BALB/c mice.
 Objectives:The objective of this research was to express and purify the recombinant scFv-PE35KDEL protein and
remove its endotoxin content, as well as to evaluate its toxicity profile by determining the LD50 and monitoring body
weight changes in BALB/c mice following injection.
Materials and Methods: After expression and purification of scFv-PE35KDEL, BALB/c mice were intraperitoneally administered single doses of 250, 500, 1000, and 2000 μg.kg-1 of immunotoxin. Mice’s weight, body temperature, and acute toxicity symptoms were evaluated every odd day for two weeks. Histopathological evaluation of the kidney, liver and lungs was performed.
Results: All mice died after a single dose of 2000 μg.kg-1 of immunotoxin, but after exposure to 1000 μg.mg-1, all mice survived for 15 days. There was no significant difference in the body temperature between the groups (p > 0.05). There was a considerable weight loss at 500 and 1000 μg.kg-1 doses until three days (p < 0.05) which recovered gradually. Diarrhea and loss of muscular tonicity were among the common adverse effects, which were worsened by increasing the dose to 1000 μg.mg-1. Based on histopathological analysis, no specific toxicity was observed in the liver and kidney tissues at doses up to 1000 μg.kg-1.
Conclusion: These findings revealed that the LD50 of scFv-PE35KDEL is in the range of 1000-2000 μg.mg-1 and it seems to be a safe and non-toxic agent, and could be a promising candidate for anti-HER2 cancer therapy. However, further in vivo evaluations are required.
کلیدواژه‌های انگلیسی مقاله breast cancer,ToxicityBreast cancer,BALB/c Mice,HER2,Immunotoxin,Pseudomonas aeruginosa,Toxicity
نویسندگان مقاله Fatemeh Saadatkhah |
1 Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Valiollah Hajhashemi |
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Azar Naimi |
Department of Pathology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Vajihe Akbari |
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Melika Kolahdoozan |
Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

نشانی اینترنتی https://www.ijbiotech.com/article_221241_44059ba5158c3939e9a4de666cf5d9f8.pdf
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