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Generation of soluble antibodies against human tissue kallikrein 7 and the evaluation of their biopharmaceutical use with a poloxamer-based hydrogel drug delivery system
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  • Ana Flavia Laureano,
  • Daniele de Araujo,
  • Chrisiane Lombello,
  • Monica Helena do Nascimento,
  • Saskia Helmsing,
  • Viola Fuehner,
  • Michael Hust,
  • Luciano Puzer
Ana Flavia Laureano
Universidade Federal do ABC
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Daniele de Araujo
Universidade Federal do ABC
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Chrisiane Lombello
Universidade Federal do ABC
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Monica Helena do Nascimento
Universidade Federal do ABC
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Saskia Helmsing
Technische Universitat Braunschweig
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Viola Fuehner
Technische Universitat Braunschweig
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Michael Hust
Technische Universitat Braunschweig
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Luciano Puzer
Universidade Federal do ABC
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Abstract

Human tissue kallikreins (KLKs) constitute a family of 15 serine proteases scattered in various tissues of the human body. They are implicated in several pathological disorders and physiological events, such as cancer, the formation of blood clot, and skin desquamation, among others, and therefore, it is believed that specific inhibitors of these enzymes may represent new therapeutic targets. KLK7 is an unusual serine protease that presents both trypsin-like and chymotrypsin-like specificity and seems to be upregulated in pathologies related to skin desquamation processes such as atopic dermatitis, psoriasis and Netherton syndrome, suggesting that this enzyme is a potential target for new therapeutic procedures. Thus, in this work, we describe the generation of recombinant IgG-like human antibodies (scFv-Fc) with high affinity for KLK7, which can be useful for detecting and neutralizing the activity of this enzyme in tissues where it appears to be upregulated. In addition, we have developed and characterized a poloxamer-based drug delivery system to encapsulate the anti-KLK7 antibodies considering the biopharmaceutical parameters of the antibodies.