a phase i dose escalation trial of vaccine replicon particles (vrp) expressing prostate-specific membrane antigen (psma) in subjects with prostate cancer：i期剂量递增试验疫苗的复制子颗粒（vrp）表达前列腺特异性膜抗原（psma）在前列腺癌者.pdf

Vaccine 31 (2013) 943–949 Contents lists available at SciVerse ScienceDirect Vaccine j o u r n a l h o m e p a g e : w w w. elsev /locate/vaccine A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer Susan F. Slovin a,∗ , Marissa Kehoe a , Robert Durso b , Celina Fernandez a , William Olson b , Jian P. Gao b , Robert Israel b , Howard I. Scher a , Stephen Morris b a Genitourinary Oncology Service, Sidney Kimmel Centerfor Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY, New York 10065, USA b Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA a r t i c l e i n f o a b s t r a c t Article history: PSMA-VRP is a propagation defective, viral replicon vector system encoding PSMA under phase I eval- Received 9 August 2012 uation for patients with castration resistant metastatic prostate cancer (CRPC). The product is derived Received in revised form from an attenuated strain of the alphavirus, Venezuelan Equine Encephalitis (VEE) virus, and incorpo- 23 November 2012 rates multiple redundant safety features. In this first in human trial, two cohorts of 3 patients with CRPC Accepted 30 November 2012 metastatic to bone were treated with up to five doses of either 0.9 × 107 IU or 0.36 × 108 IU of PSMA-VRP Available online 13 December 2012 at weeks 1, 4, 7, 10 and 18, f