Phase I Study of P-cadherin-targeted Radioimmunotherapy with Y-FF-21101 Monoclonal Antibody in Solid Tumors.

Purpose: Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors.

Patients And Methods: The safety and efficacy of Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors ( = 15) over a dose range of 5-25 mCi/m.

Preclinical Characterization of the Radioimmunoconjugate In or Y-FF-21101 Against a P-Cadherin-Expressing Tumor in a Mouse Xenograft Model and a Nonhuman Primate.

P-cadherin is overexpressed in various cancers and can be a target for radioimmunotherapy. We investigated the preclinical pharmacokinetics and pharmacology of FF-21101, an In- or Y-conjugated monoclonal antibody against P-cadherin, to evaluate its clinical applications. The radiochemical purity, binding affinity, and in vitro serum stability of In or Y-labeled FF-21101 were evaluated.

Designation of enzyme activity of glycine-N-acyltransferase family genes and depression of glycine-N-acyltransferase in human hepatocellular carcinoma.

The human glycine-N-acyltransferase (hGLYAT) gene and two related-genes (GLYATL1 and GLYATL2) were isolated. Human GLYAT, GLYATL1, and GLYATL2 cDNAs were isolated and shown to encode polypeptides of 295, 302, and 294 amino acids, respectively. GLYAT catalyzes glycine-N-acyltransfer reaction with benzoyl-CoA acting as a typical aralkyl transferase, while GLYATL1 catalyzed glutamine-N-acyltransfer reaction with phenylacetyl-CoA as an arylacetyl transferase.