Generation of soluble antibodies against human tissue kallikrein 7 and
the evaluation of their biopharmaceutical use with a poloxamer-based
hydrogel drug delivery system
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.