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.