Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients

Targeting the GA733 antigen (also known ar,CO 17-1A, EGP, KS1-4, KSA, Ep CA M) by monoclonal antibody C017-1A or anti-idiotypic antibodies mimicking th e CO17-1A or GA733 epitope has induced prolonged survival and specific immu ne responses to the antigen, respectively, in colorectal cancer (CRC) patie nts. In pre-clinical studies in mice and rabbits, recombinant baculovirus d erived GA733-2E antigen was superior to anti-idiotypic antibodies at modula ting specific immune responses. Our aim was to evaluate the immunogenicity and potential toxicity of alum-precipitated GA733-2E in a phase I trial in patients with resected CRC or pancreatic cancer. Six patients with advanced pancreatic carcinoma and 6 with CRC Dukes' stage A, B or C received betwee n 4 and 7 doses of alum-precipitated GA733-2E at 50, 200 or 800 mug/dose at monthly intervals. Antibody binding to GA733-2E or antigen-positive CRC ce lls was determined, as were antigen-specific proliferative, cytolytic T-Iym phocyte and delayed-type hyper-sensitivity responses. Six of the 12 patient s developed antigen-specific humoral immune responses after immunotherapy, and 8 developed cellular immune responses. The overall immune response rate , including patients with humoral and/or cellular immune responses, was 83% , Median overall survival of the CRC and pancreatic cancer patients was 39. 8 and 11.2 months, respectively, Following 18 years of single-epitope targe ting of the GA733 antigen, immunization of patients against multiple epitop es of the antigen frequently induces an immune response in the absence of s ignificant toxicity, despite relatively widespread expression of this antig en on normal epithelial cells. (C) 2001 Wiley-Liss, Inc.