G17DT - a new weapon in the therapeutic armoury for gastrointestinal malignancy

G17DT or Gastrimmune, as it was formally known, is an antigastrin 17 immuno gen producing neutralising high affinity antibodies directed against gastri n-17 (G17). Preclinical studies, initiated to identify biological functiona lity of G17DT-induced antibodies, confirmed that the antibodies both reduce d G17 stimulated gastric acid secretion and inhibited gastrin from interact ing with the CCK-2 receptor. Therapeutic efficacy of both passive and activ e immunisation with G17DT has been established in a number of tumour system s including both primary and metastatic disease. Furthermore, additive effe cts with 5-fluorouracil (5-FU)/leucovorin have been confirmed in both colon and gastric turnout models. Phase I/II studies in advanced gastrointestina l (GI) malignancies have shown no systemic or autoimmune reactions to activ e immunisation with G17DT. Use of an optimised dose has yielded a high prop ortion of responders (> 80%), with minimal side effects and antibody titres measurable within 2 - 4 weeks. Taken together these results suggest that t he G17DT immunogen is a promising agent for the treatment of GI cancer and Phase III trials, currently underway, will definitively evaluate this early promise.