G17DT--a new weapon in the therapeutic armoury for gastrointestinal malignancy.
G17DT or Gastrimmune, as it was formally known, is an antigastrin 17 immunogen producing neutralising high affinity antibodies directed against gastrin-17 (G17). Preclinical studies, initiated to identify biological functionality of G17DT-induced antibodies, confirmed that the antibodies both reduced G17 stimulated gastric acid secretion and inhibited gastrin from interacting with the CCK-2 receptor. Therapeutic efficacy of both passive and active immunisation with G17DT has been established in a number of tumour systems including both primary and metastatic disease. Furthermore, additive effects with 5-fluorouracil (5-FU)/leucovorin have been confirmed in both colon and gastric tumour models. Phase I/II studies in advanced gastrointestinal (GI) malignancies have shown no systemic or autoimmune reactions to active immunisation with G17DT. Use of an optimised dose has yielded a high proportion of responders (> 80%), with minimal side effects and antibody titres measurable within 2-4 weeks. Taken together these results suggest that the G17DT immunogen is a promising agent for the treatment of GI cancer and Phase III trials, currently underway, will definitively evaluate this early promise.
Watson
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SA
Academic Unit of Cancer Studies, Division of GI Surgery, University of Nottingham, QMC, University Hospital, Nottingham, NG7 2UH, UK. sue.watson@nottingham.ac.uk
Gilliam
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AD
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004168:Diphtheria Toxoid / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D005755:Gastrins / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D000906:Antibodies; D000941:Antigens; D019496:Cancer Vaccines; D004168:Diphtheria Toxoid; D005755:Gastrins; C482698:gastrin immunogen; C013550:gastrin 17