Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer.
Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy.
Tagawa
Scott T
ST
Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY, USA. stt2007@med.cornell.edu
Beltran
Himisha
H
Vallabhajosula
Shankar
S
Goldsmith
Stanley J
SJ
Osborne
Joseph
J
Matulich
Dan
D
Petrillo
Kristen
K
Parmar
Sarojben
S
Nanus
David M
DM
Bander
Neil H
NH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D051379:Mice; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C478680:J591 monoclonal antibody; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D017430:Prostate-Specific Antigen