ABSTRACT
AIM: The aim of this study was to determine the ability of G17DT to generate anti-gastrin antibodies in jaundiced patients with biliary obstruction due to advanced pancreatic cancer. METHODS: G17DT was administered to 41 patients with advanced pancreatic adenocarcinoma by intramuscular (i.m.) injection at a dose of 250mcg at weeks 0, 1 and 3 of the study. RESULTS: Thirty-five of 41 patients participating in the study were categorized as responders in terms of their gastrin-17 antibody response. There was no correlation between the maximum G17 antibody response and the bilirubin level at either week 0 or week 12. The median survival of patients from the time of the first injection of G17DT was 204 days with 25% of patients surviving for
Subject(s)
Adenocarcinoma/drug therapy , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Gastrins/immunology , Immunization , Jaundice/immunology , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/immunology , Adult , Aged , Aged, 80 and over , Antibody Formation/drug effects , Bilirubin/blood , Cancer Vaccines/adverse effects , Cancer Vaccines/blood , Cholestasis/immunology , Disease Progression , Female , Gastrins/adverse effects , Gastrins/blood , Gastrins/therapeutic use , Humans , Immunization/adverse effects , Injections, Intramuscular , Male , Middle Aged , Pancreatic Neoplasms/immunology , Survival Analysis , Time Factors , Treatment Outcome , United KingdomABSTRACT
PURPOSE: G17DT is a gastrin immunogen, raising antibodies that blockade gastrin-stimulated growth. The aim of the study was to characterise antibody response and assess safety and tolerability of G17DT given to patients with gastric cancer. EXPERIMENTAL DESIGN: G17DT was administered to 52 patients with gastric adenocarcinoma at weeks 0, 2 and 6 by intramuscular injection at doses of 10, 100 and 250 microg. Antibody levels were measured by an ELISA assay. A radioligand displacement assay determined the ability of G17DT-immunised patients' sera to inhibit binding of 125IG17 to cholecystokinin (CCK)-2 receptors. RESULTS: By week 12 of the study, 6/12 evaluable stage I-III patients achieved an antibody response in the 10 microg group, 7/11 in the 100 microg group, and 11/12 in the 250 microg group. Stage IV patients dosed at 250 microg achieved a similar response rate to stage I-III patients dosed at 10 or 100 microg. G17DT was well tolerated in 47/52 patients. Two patients suffered significant adverse reactions including injection site pain and abscess. G17DT antibodies displaced iodinated gastrin from CCK-2 receptors, with the level of displacement correlating with antibody titre. CONCLUSIONS: G17DT immunisation is a well-tolerated method of raising functional antibodies to 17 amino acid gastrin forms in patients with gastric carcinomas.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/immunology , Antibody Formation/drug effects , Cancer Vaccines/administration & dosage , Gastrins , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cancer Vaccines/adverse effects , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Immune Sera/drug effects , Immune Sera/immunology , Immunization, Secondary , Injections, Intramuscular , Male , Middle Aged , Neoplasm Staging , Receptor, Cholecystokinin B/drug effects , Receptor, Cholecystokinin B/immunology , Statistics as Topic , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
OBJECTIVES: We have previously reported the ability of D17DT (formerly GnRH-DT) vaccination to produce castrate levels of androgens in men with advanced prostate cancer. This study examines the efficacy and tolerability of 3 and 15 micrograms of D17DT in 12 patients with advanced prostate cancer to establish a dose-response relationship. METHODS: 12 patients received either 3 or 15 micrograms of D17DT as 3 deep intramuscular injections over 6 weeks. Outcome was assessed in terms of physical and biochemical evaluations of clinical progression and antibody titres. RESULTS: Significant titres of anti-GnRH antibodies were detected in 2 out of 6 subjects who received 15 micrograms of D17DT; suppression of testosterone to castrate levels accompanied by a significant and prolonged reduction in PSA was also demonstrated. No responses were seen following treatment with 3 micrograms of D17DT. CONCLUSION: The induction of anti-GnRH antibodies through vaccination with 15 micrograms D17DT can produce and sustain castrate levels of testosterone in men with advanced prostate cancer.
Subject(s)
Cancer Vaccines/administration & dosage , Diphtheria Toxoid/immunology , Gonadotropin-Releasing Hormone/immunology , Oligopeptides/immunology , Prostatic Neoplasms/prevention & control , Androgen Antagonists/therapeutic use , Cancer Vaccines/immunology , Diphtheria Toxoid/chemistry , Disease Progression , Dose-Response Relationship, Drug , Gonadotropin-Releasing Hormone/chemistry , Humans , Male , Oligopeptides/chemistry , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Testosterone/bloodABSTRACT
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.
Subject(s)
Antibodies, Neoplasm/immunology , Cancer Vaccines/immunology , Gonadotropin-Releasing Hormone/immunology , Immunotoxins/immunology , Prostatic Neoplasms/immunology , Testosterone/blood , Aged , Antibodies, Neoplasm/biosynthesis , Antibodies, Neoplasm/blood , Cancer Vaccines/administration & dosage , Cancer Vaccines/adverse effects , Diphtheria Toxoid/administration & dosage , Diphtheria Toxoid/immunology , Dose-Response Relationship, Drug , Humans , Immunotherapy, Active , Immunotoxins/administration & dosage , Immunotoxins/adverse effects , Injections, Intramuscular , Male , Pilot Projects , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/therapyABSTRACT
The growth and structure of a virus-induced tumour has been studied in normal and immunised animals. Retardation of tumour growth in immunised animals is accompanied by a lymphoreticular infiltrate; macrophages ingest apparently intact tumour cells.