Anti-FGF23 is now assessed by clinical trials for treating X-linked hypophosphatemia
X-linked hypophosphatemia (XLH) is a heritable form of rickets that results from mutations in the gene encoding the phosphate regulating endopeptidase (PHEX
). Unlike diet-associated forms of rickets, XLH cannot be ameliorated by vitamin D ingestion. XLH patients have increased serum levels of FGF23, which decreases both inorganic phosphate (Pi) and the activated form of vitamin D. In this issue of the Journal of Clinical Investigation
, Thomas Carpenter and colleagues at Yale University evaluated the effectiveness and safety of an anti-FGF23 antibody (KRN23) in a small cohort of XLH patients. A single dose of KRN23 administered intravenously (i.v.) or subcutaneously (s.c.) improved renal phosphate reabsorption, and increased serum Pi and activated vitamin D concentrations, and s.c. administration provided benefit for a longer duration than i.v. dosing. These findings, along with a favorable safety profile, indicate that KRN23 should be further evaluated for use in XLH patients.
Altered glycosylation patterns protect tumors from NK cells
Compared to other diseased cells, malignant tumor cells often exhibit modified surface glycosylation patterns, potentially altering recognition by host immune cells. Natural killer (NK) cells are sentinels of cancer immunosurveillanc system and express multiple receptors that allow for discrimination between healthy and malignant cells. In this issue of the , Stephan von Gunten and colleagues at the University of Bern determined that ligands of the inhibitory sialic acid-binding lectins Siglec-7 and Siglec-9 are expressed on the surface of multiple tumor cell types, and that expression of these ligands protects tumor cells from NK cell responses. Evaluation of NK cells in healthy donors revealed the presence of a Siglec-9-expressing cytotoxic NK cell population with enhanced chemotactic potential. Interestingly, the Siglec-9-expressing NK cell population was reduced in peripheral blood from patients with colon adenocarcinoma and malignant melanoma. These data suggest that targeting Siglec-7 and Siglec-9 ligands may enhance NK cell-based cancer therapies.