title: Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer.
abstract: D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 microg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 microg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders.
authors.affiliation: Department of Urology, City Hospital, Nottingham, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Simms
authors.forename: D P
authors.initials: DP
authors.lastname: Scholfield
authors.forename: E
authors.initials: E
authors.lastname: Jacobs
authors.forename: D
authors.initials: D
authors.lastname: Michaeli
authors.forename: P
authors.initials: P
authors.lastname: Broome
authors.forename: J E
authors.initials: JE
authors.lastname: Humphreys
authors.forename: M C
authors.initials: MC
authors.lastname: Bishop
mesh_terms: D000368:Aged; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D013739:Testosterone / Q000097:blood*
chemical_list: D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D004168:Diphtheria Toxoid; D000922:Immunotoxins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen