TY - JOUR
T1 - Targeted Systemic Therapy of Prostate Cancer With a Monoclonal Antibody to Prostate-Specific Membrane Antigen
AU - Bander, Neil H.
AU - Nanus, David M.
AU - Milowsky, Matthew I.
AU - Kostakoglu, Lale
AU - Vallabahajosula, Shankar
AU - Goldsmith, Stanley J.
N1 - Funding Information:
Supported in part by NIH General Clinical Research Centers Program (NCRR Grant No. M01RR00047); US Department of Army (DAMD17-98-1-8594), Cancer Research Institute, Cap Cure, the David H. Koch Foundation, the Peter Sacerdote Foundation, BZL Biologics, Inc, and Millennium Pharmaceuticals, Inc. N.H.B. developed the J591 antibody used in this study. J591 and related anti-PSMA ext antibody patents were assigned to the Cornell Research Foundation and subsequently licensed to BZL Biologics, Inc. N.H.B. is a paid consultant to BZL Biologics, Inc.
PY - 2003/10
Y1 - 2003/10
N2 - 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 β-emitting radiometals yttrium 90 and lutetium 177, and a third using a cytotoxin (DMI) linked to J591. Imaging of patients after they have received radiolabeled J591 demonstrates excellent tumor targeting.
AB - 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 β-emitting radiometals yttrium 90 and lutetium 177, and a third using a cytotoxin (DMI) linked to J591. Imaging of patients after they have received radiolabeled J591 demonstrates excellent tumor targeting.
UR - https://www.scopus.com/pages/publications/0142030952
U2 - 10.1016/S0093-7754(03)00358-0
DO - 10.1016/S0093-7754(03)00358-0
M3 - Article
C2 - 14571414
AN - SCOPUS:0142030952
SN - 0093-7754
VL - 30
SP - 667
EP - 676
JO - Seminars in Oncology
JF - Seminars in Oncology
IS - 5
ER -