Clinical Use of Monoclonal Antibody HuJ591 Therapy: Targeting Prostate Specific Membrane Antigen

Abstract

Prostate specific membrane antigen (PSMA) is a cell surface peptidase highly expressed by malignant prostate epithelial cells and vascular endothelial cells of numerous solid tumor malignancies but not normal vascular endothelium in benign tissues or neoplastic epithelial cells of nonprostate malignancies. Monoclonal antibody (mAb) J591 recognizes the extracellular domain of PSMA. The current status of clinical trials using mAb J591 is reviewed. The mouse antibody was deimmunized by replacing murine immunoglobulin sequences with human immunoglobulin sequences, resulting in a nonimmunogenic antibody HuJ591. Results of completed and ongoing phase 1 and 2 clinical trials using mAb J591 are presented. A phase I clinical trial with murine J591 indicated that it possesses high affinity for prostate cancer metastases in bone and soft tissue. A phase I clinical trial showed that HuJ591 was well tolerated, demonstrated excellent targeting to disseminated prostate cancer sites and did not result in a host immune response to the antibody. A phase II clinical trial was initiated to study the efficacy of combining HuJ591 with low dose interleukin-2. Two phase I studies in patients with prostate cancer are in progress using the beta-emitting radiometals 90yttrium and 177lutetium linked via a DOTA chelate to HuJ591. Preliminary results from an ongoing phase I trial of 111indium labeled mAb HuJ591 in patients with advanced solid tumors showed that HuJ591 specifically targets nonprostate cancers. Early results of clinical studies indicate that mAb HuJ591 represents targeted therapy to PSMA and has therapeutic potential in prostate cancer and other urological and solid tumor malignancies.