In this article, we will discuss Kepivance™ (Mechanism of Action). So, let’s get started.
Keratinocyte growth factor (KGF) is an endogenous protein in the fibroblast growth
factor (FGF) family that binds to the KGF receptor. Binding of KGF to its receptor has
been reported to result in proliferation, differentiation, and migration of epithelial cells.
The KGF receptor, one of four receptors in the FGF family, has been reported to be
present on epithelial cells in many tissues examined including the tongue, buccal mucosa, esophagus, stomach, intestine, salivary gland, lung, liver, pancreas, kidney, bladder, mammary gland, skin (hair follicles and sebaceous gland), and the lens of the eye. The KGF receptor has been reported to not be present on cells of the hematopoietic lineage.
Endogenous KGF is produced by mesenchymal cells and is upregulated in response to epithelial tissue injury.
In mice and rats, Kepivance™ enhanced proliferation of epithelial cells (as measured by Ki67 immunohistochemical staining and BrDU uptake) and demonstrated an increase in tissue thickness of the tongue, buccal mucosa and gastrointestinal tract. Kepivance™ has been studied in murine models of chemotherapy and radiation-induced gastrointestinal injury. In such models, administration of Kepivance™ prior to and/or after the cytotoxic insult improved survival and reduced weight loss compared to control animals.
Kepivance™ has been shown to enhance the growth of human epithelial tumor cell lines
in vitro at concentrations ≥ 10 mcg/mL (> 15-fold higher than average therapeutic
concentrations in humans). In nude mouse xenograft models, three consecutive daily
treatments of Kepivance™ at doses of 1,500 and 4,000 mcg/kg (25- and 67-fold higher
than the recommended human dose, respectively) repeated weekly for 4 to 6 weeks were associated with a dose-dependent increase in the growth rate of 1 of 7 KGF receptor-expressing human tumor cell lines.