Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen

Semin Oncol. 2003 Oct;30(5):667-76. doi: 10.1016/s0093-7754(03)00358-0.


For the last 60 years, hormonal therapy has been the cornerstone of treatment of metastatic prostate cancer. Unfortunately, hormonal therapy is purely palliative and improved systemic therapies are necessary. Monoclonal antibodies (mAbs) have proven valuable in the treatment of several diseases including cancer. mAbs act by focusing an immune response on or by targeting delivery of highly cytotoxic agents to the cancer cells without targeting normal cells. Prostate-specific membrane antigen (PSMA) has been identified as an ideal antigenic target in prostate cancer. PSMA is the most well-established, highly restricted prostate cancer cell surface antigen. It is expressed at high density on the cell membrane of all prostate cancers, and after antibody binding, the PSMA-antibody complex is rapidly internalized along with any payload carried by the antibody. J591 is the first IgG mAb developed to target the extracellular domain of PSMA, and it has been deimmunized (humanized) to allow repeated dosing in patients. Three phase I studies are in progress, two using the beta-emitting radiometals yttrium 90 and lutetium 177, and a third using a cytotoxin (DM1) linked to J591. Imaging of patients after they have received radiolabeled J591 demonstrates excellent tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody Affinity / immunology
  • Antigens, Surface / immunology
  • Clinical Trials, Phase I as Topic
  • Cytotoxins / administration & dosage
  • Disease Models, Animal
  • Drug Delivery Systems / methods
  • Drug Evaluation, Preclinical
  • Extracellular Space / drug effects
  • Extracellular Space / immunology
  • Fluorescent Antibody Technique
  • Glutamate Carboxypeptidase II / antagonists & inhibitors*
  • Glutamate Carboxypeptidase II / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Lutetium / administration & dosage
  • Male
  • Mice
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • Radioimmunodetection
  • Radioisotopes / administration & dosage
  • Treatment Outcome
  • Yttrium Radioisotopes / administration & dosage


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Cytotoxins
  • Immunoglobulin G
  • J591 monoclonal antibody
  • Radioisotopes
  • Yttrium Radioisotopes
  • Lutetium
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II